Obesity and Cancer S. Lani Park November 30, 2009.

Obesity and CancerObesity and Cancer

S. Lani ParkS. Lani Park

November 30, 2009November 30, 2009

Presentation OutlinePresentation Outline Epidemiology of obesityEpidemiology of obesity Measuring adiposityMeasuring adiposity Overview of body weight and cancerOverview of body weight and cancer Potential pathwaysPotential pathways Site specific examplesSite specific examples

BreastBreast ColonColon ProstateProstate Endometrial cancerEndometrial cancer Lung and UADT cancerLung and UADT cancer

U.S. Obesity U.S. Obesity TrendsTrends

Obesity, globallyObesity, globally International Association for the Study of International Association for the Study of

Obesity estimated in 2007 ~40-50% of Obesity estimated in 2007 ~40-50% of men and 25%-35% of women in EU men and 25%-35% of women in EU were overweight (25-29.9 kg/mwere overweight (25-29.9 kg/m22)) Additional 15-25% of men and women Additional 15-25% of men and women

were obese.were obese. WHO’s latest projections for 2005:WHO’s latest projections for 2005:

Globally, ~ 1.6 billion adults (age Globally, ~ 1.6 billion adults (age 15+) were overweight; 15+) were overweight;

at least 400 million adults were at least 400 million adults were obese. obese.

Projects that by 2015, approximately 2.3 Projects that by 2015, approximately 2.3 billion adults will be overweight and billion adults will be overweight and more than 700 million will be obese.more than 700 million will be obese.

At least 20 million children under the At least 20 million children under the age of 5 years are overweight globally in age of 5 years are overweight globally in 2005.2005.

Not just a problem in high income Not just a problem in high income countriescountries

BMI and mortalityBMI and mortality

Prospective Studies Collaboration, Lancet, 2009

Risk factors for obesityRisk factors for obesity

Energy imbalanceEnergy imbalance GeneticsGenetics MetabolismMetabolism Behavior Behavior EnvironmentEnvironment CultureCulture Socioeconomic statusSocioeconomic status

Components of body weightComponents of body weight

Subcutaneous fatSubcutaneous fat Gluteofemoral Gluteofemoral

Visceral fat (abdominal fat) Visceral fat (abdominal fat) Excess of visceral fat can be termed as central obesity. Excess of visceral fat can be termed as central obesity.

AdiposeAdipose

Males:Males:Total fat 15%= Total fat 15%=

3% essential + 12% 3% essential + 12% storagestorage

Females:Females:Total fat 27%= Total fat 27%=

12% essential + 15% 12% essential + 15% storagestorage

Lean Body Mass Lean Body Mass MuscleMuscle

45% Males45% Males36% Female36% Female

BoneBone

15% male15% male

12 % female12 % female

OtherOther

25%25%

Types of fat:Types of fat:

NOTE: Components of body weight changes NOTE: Components of body weight changes with agewith age

Measuring AdiposityMeasuring AdipositySkinfold thickness using calipers:Skinfold thickness using calipers: Calipers are used to measure the thickness of skinfold on Calipers are used to measure the thickness of skinfold on

areas of the triceps, biceps, subscapular, abdomen and areas of the triceps, biceps, subscapular, abdomen and thighs.thighs.

Used to indirectly assess body fat distributions.Used to indirectly assess body fat distributions. Can have inter-observer variationCan have inter-observer variation Ability of skinfold thickness to predict morbidity and Ability of skinfold thickness to predict morbidity and

mortality not well established.mortality not well established.

Bioelectrical ImpedanceBioelectrical Impedance Measures the resistance of body tissues to the flow of an Measures the resistance of body tissues to the flow of an

undetectable low-voltage electrical current. undetectable low-voltage electrical current. Typically, people stand barefoot on metal footplates, and Typically, people stand barefoot on metal footplates, and

the electrical current is sent up one foot and down the the electrical current is sent up one foot and down the other. other.

Based on principle that lean body mass or water has lower Based on principle that lean body mass or water has lower resistance to current. By measuring the resistance to the resistance to current. By measuring the resistance to the current, doctors can estimate the percentage of body fat. current, doctors can estimate the percentage of body fat.

Test takes only about 1 minute. Test takes only about 1 minute.

Measuring AdiposityMeasuring AdiposityAnthropometryAnthropometryHeight, Weight, and BMIHeight, Weight, and BMI Weight: adulthood weight gain (age 18 to 55) Weight: adulthood weight gain (age 18 to 55)

usually reflects an increase in body fat.usually reflects an increase in body fat. Body Mass Index (BMI, kg/mBody Mass Index (BMI, kg/m22): highly ): highly

correlated with both absolute body fat and correlated with both absolute body fat and percent body fat. percent body fat. WHO categories WHO categories

http://apps.who.int/bmi/index.jsphttp://apps.who.int/bmi/index.jsp: : Normal: 18.5-24.9 kg/mNormal: 18.5-24.9 kg/m22

Overweight: 25-29.9 kg/mOverweight: 25-29.9 kg/m22 Obese: ≥ 30 kg/mObese: ≥ 30 kg/m22

Disadvantages: Disadvantages: Doesn’t differentiate between body compartments. Doesn’t differentiate between body compartments. Not accurate between changes in lean body mass Not accurate between changes in lean body mass

and height. and height. Variations in ethnicity (Variations in ethnicity (

http://www.who.int/nutrition/publications/bmi_asia_shttp://www.who.int/nutrition/publications/bmi_asia_strategies.pdftrategies.pdf ) )

Measuring AdiposityMeasuring AdiposityWaist-Hip-Ratio (WHR):Waist-Hip-Ratio (WHR): Measure for central obesityMeasure for central obesity Higher correlation with visceral adipose tissueHigher correlation with visceral adipose tissue Abdominal obesity cut-offs Abdominal obesity cut-offs ((Expert Panel on the Identification Evaluation and Treatment of Overweight and Obesity in Adults

(1998))::

102 cm in men or 0.95 WHR102 cm in men or 0.95 WHR 88 cm in women or 0.80 WHR 88 cm in women or 0.80 WHR

Self-report can be challenging.Self-report can be challenging.

Dilution method (hydrometry):Dilution method (hydrometry): Measures total body water using isotopes.Measures total body water using isotopes. Based on principle that total body water to fat Based on principle that total body water to fat

free mass ratio is stable (~0.73).free mass ratio is stable (~0.73). Ratio may not be accurate in patients who are Ratio may not be accurate in patients who are

ill.ill.

Measuring AdiposityMeasuring AdiposityDensitometry (Underwater weighing):Densitometry (Underwater weighing): Use to be the gold standard. Use to be the gold standard. Based on principle that fat tissue is lighter Based on principle that fat tissue is lighter

than fat-free tissue. than fat-free tissue. People are weighed underwater in a small People are weighed underwater in a small

pool. pool. Although this method is considered accurate, Although this method is considered accurate, Requires special equipment, considerable Requires special equipment, considerable

time, and expertise totime, and expertise toAir-displacement plethysmography (ADP)Air-displacement plethysmography (ADP) Using air rather than water displacement for Using air rather than water displacement for

measuring body volume and density.measuring body volume and density. Quick and more comfortable than being Quick and more comfortable than being

submerged in water.submerged in water.

Measuring AdiposityMeasuring AdiposityDXA: Dual energy X-ray absorptiometryDXA: Dual energy X-ray absorptiometry This imaging procedure accurately This imaging procedure accurately

determines the amount and distribution of determines the amount and distribution of body fat. DEXA uses a very low dose of body fat. DEXA uses a very low dose of radiation and is safe. radiation and is safe.

Estimates fat-free mass, fat mass, and bone Estimates fat-free mass, fat mass, and bone mineral density.mineral density.

Limitations, expensive and time consuming.Limitations, expensive and time consuming. Cannot distinguish from visceral and Cannot distinguish from visceral and

subcutaneous fat.subcutaneous fat.CT or MRI CT or MRI Can assess body composition and fat Can assess body composition and fat

distribution at a tissue-organ level.distribution at a tissue-organ level. CT has a high radiation exposure. CT has a high radiation exposure. Very ExpensiveVery Expensive Usually harder to accommodate morbidly Usually harder to accommodate morbidly

obese people.obese people.

Renehan, 2008Renehan, 2008

Cancer types associated with Cancer types associated with increased BMIincreased BMI

van Kruijsdijk RCM C, CEBP, 2009van Kruijsdijk RCM C, CEBP, 2009

van Kruijsdijk RCM C, CEBP, 2009van Kruijsdijk RCM C, CEBP, 2009

Potential pathways Potential pathways linking obesity with linking obesity with cancercancer

IGF and Insulin pathwayIGF and Insulin pathway

Calle EE, Kaaks R. Nature, 2004

Things to consider when Things to consider when studying BMI in cancerstudying BMI in cancer

Reverse causalityReverse causality Confounding variables Confounding variables Ethnic differencesEthnic differences Self report validity, information biasSelf report validity, information bias

Validity of self-reported height Validity of self-reported height and weightand weight

Hu FB, Obesity Epidemiology

Conceptual Conceptual meanings of meanings of Statistical Models Statistical Models using using anthropometric anthropometric variables to variables to predict disease predict disease riskrisk


Factors to consider when Factors to consider when investigating body weight investigating body weight

changechange Reverse causalityReverse causality Confounding Confounding

variablesvariables Ethnic differencesEthnic differences Self report validity, Self report validity,

information biasinformation bias Energy BalanceEnergy Balance

Food consumptionFood consumption Physical ActivityPhysical Activity

CollinearityCollinearity

Energy Balance Energy Balance The balance between energy taken in, The balance between energy taken in,

generally by food and drink, and energy generally by food and drink, and energy expended. expended.

Energy expenditure is influenced by Energy expenditure is influenced by genetics, body size and amount of muscle, genetics, body size and amount of muscle, and by physical activity. and by physical activity.

While calories are probably the most While calories are probably the most critical element in maintaining your energy critical element in maintaining your energy balance, other factors in your diet such as balance, other factors in your diet such as how much fiber or calcium you eat may how much fiber or calcium you eat may influence your energy expenditure and how influence your energy expenditure and how much muscle and fat you have. much muscle and fat you have.

Vaughn P, www.cancer.gov

Example of Semi-quantitative Example of Semi-quantitative FFQFFQDIETARY HABITS [Example, will need to adapt to each country]

How often did you consume the following foods and beverages one year ago?

UnitUnit Food item Food item How many times per day, week, How many times per day, week, month, year? (mark one column month, year? (mark one column only)only)

dayday weekweek montmonthh

yearyear NeverNever

D1D1 1 portion1 portion BeefBeef |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D2D2 1 portion 1 portion PorkPork |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D3D3 1 portion 1 portion PoultryPoultry |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D4D4 1 portion 1 portion Other meat (lamb, etc.)Other meat (lamb, etc.) |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D5D5 1 portion1 portion FishFish |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D6D6 1 portion1 portion Ham, salami, sausagesHam, salami, sausages |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D7D7 1 portion 1 portion Raw green vegetables and Raw green vegetables and saladssalads

|__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D8D8 1 portion1 portion Cooked green vegetablesCooked green vegetables |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D9D9 1 portion1 portion CarrotsCarrots |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D10D10 1 portion1 portion Fresh tomatoesFresh tomatoes |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

D11D11 1 portion1 portion Pulses (peas, beans, etc.)Pulses (peas, beans, etc.) |__|__||__|__| |__|__||__|__| |__|__||__|__| |__|__||__|__| |__||__|

Example of a FFQExample of a FFQ

Physical ActivityPhysical Activity

metabolic equivalents of energy expenditure (METs) metabolic equivalents of energy expenditure (METs) METs= (sleeping [h/d]*0.91 + sitting [h/d]*1.0+ light activity METs= (sleeping [h/d]*0.91 + sitting [h/d]*1.0+ light activity [h/d]*2.4 + moderate activity [h/d]*4.0 + vigorous activity [h/d]*2.4 + moderate activity [h/d]*4.0 + vigorous activity [h/d]*7.2)/24) [h/d]*7.2)/24)

Cancer site-specific Cancer site-specific examplesexamples

BreastBreastColonColonProstateProstateEndometrEndometrialialUADTUADTLungLung

Breast cancer, overviewBreast cancer, overview Most common cancer Most common cancer

among femalesamong females 192,370 estimated 192,370 estimated

newly incident female newly incident female cases, 2009cases, 2009

40,170 estimated 40,170 estimated female deaths, 2009female deaths, 2009

Survival rate by stageSurvival rate by stage ~96% among localized~96% among localized ~84% for regional~84% for regional ~27% for distant~27% for distant

African-American African-American women younger than 50 women younger than 50 years of age have a years of age have a higher age-specific higher age-specific incidence than White incidence than White womenwomen

Risk FactorsRisk Factors AgeAge GeneticsGenetics RaceRace Hormones Hormones

Nulliparity, late age of Nulliparity, late age of parity, early menarche.parity, early menarche.

ObesityObesity Benign breast diseaseBenign breast disease DietDiet AlcoholAlcohol Smoking?Smoking? Gale ModelGale Model

http://http://www.cancer.gov/www.cancer.gov/bcrisktool/bcrisktool/

Renehan, 2008

WHR and breast cancer, WHR and breast cancer, postmenopausal womenpostmenopausal women

Harvie, 2003

WHR and breast cancer, premenopausal WHR and breast cancer, premenopausal womenwomen

Harvie, 2003

Breast Cancer and Obesity Breast Cancer and Obesity summarysummary

In general, BMI and body weight is positively In general, BMI and body weight is positively associated with postmenopausal breast cancer associated with postmenopausal breast cancer and inversely associated with premenopausal and inversely associated with premenopausal breast cancerbreast cancer

Weight gain has also been associated with Weight gain has also been associated with greater risk of post-menopausal breast cancer.greater risk of post-menopausal breast cancer.

This effect may be modified by HRT use.This effect may be modified by HRT use. After adjustment for BMI, associations After adjustment for BMI, associations

between WHR and breast cancer are between WHR and breast cancer are attenuated.attenuated.

Implicated pathways include:Implicated pathways include: EstrogenEstrogen IGF-1IGF-1

Inverse relationship found in premenopausal Inverse relationship found in premenopausal women may be a result of lower circulating women may be a result of lower circulating sex steroid hormones. sex steroid hormones.

Colon Cancer, overviewColon Cancer, overview Third most common Third most common

cancer among men and cancer among men and womenwomen

106,100 estimated cases 106,100 estimated cases for 2009for 2009

49,920 estimated deaths49,920 estimated deaths 5-year survival rate:5-year survival rate:

90% localized90% localized 68% regional68% regional 11% distant11% distant

African Americans and African Americans and Ashkenazi Jews have Ashkenazi Jews have one of the highest one of the highest incidencesincidences

Risk factorsRisk factors AgeAge Colon polypsColon polyps GeneticsGenetics Race/ethnicityRace/ethnicity History of bowel History of bowel

diseasedisease ObesityObesity DietDiet AlcoholAlcohol Smoking Smoking Type 2 DiabetesType 2 Diabetes

Colon Cancer and Colon Cancer and ObesityObesity

Harriss DJ, 2008

Pischon, 2008

WHR and WHR and Colon CancerColon Cancer

BMI and BMI and Colon CancerColon Cancer

Obesity and colorectal cancers, Obesity and colorectal cancers, summarysummary

In 2002-03 IARC concluded there is sufficient In 2002-03 IARC concluded there is sufficient evidence that obesity is associated with an evidence that obesity is associated with an increased risk in colo-rectal cancer.increased risk in colo-rectal cancer.

This relationship is stronger among men than This relationship is stronger among men than women.women.

Possibly because body weight and fat Possibly because body weight and fat distribution differs between men and women. distribution differs between men and women. This hypothesis is supported by findings from EPIC, This hypothesis is supported by findings from EPIC,

that WHR is strong risk factor for colon cancer.that WHR is strong risk factor for colon cancer. Further support: association between C-peptide Further support: association between C-peptide

and colon cancer. C-peptide is correlated with and colon cancer. C-peptide is correlated with visceral fat accumulation.visceral fat accumulation.

Evidence in rectal cancer is inconclusive.Evidence in rectal cancer is inconclusive. Potential pathways:Potential pathways:

HyperinsulemiaHyperinsulemia IGF-1IGF-1 Adipokines and hormones.Adipokines and hormones.

Prostate Cancer, Prostate Cancer, overviewoverview

Most common cancer Most common cancer among men.among men.

192,280 estimated 192,280 estimated cases for 2009cases for 2009

27,360 estimated 27,360 estimated deaths for 2009deaths for 2009

Average 5 year Average 5 year survival rate:survival rate: ~over 99% localized ~over 99% localized

and regionaland regional ~32% distant~32% distant

African-American men African-American men are also more likely to are also more likely to be diagnosed at an be diagnosed at an advanced stage advanced stage

Risk FactorsRisk Factors Age Age

Lifetime probability of Lifetime probability of prostate cancer 1 in 6 prostate cancer 1 in 6

RaceRace Geographical regionGeographical region Family HistoryFamily History Genetics (8q24)Genetics (8q24) Diet?Diet? Obesity?Obesity? Infection?Infection? Smoking?Smoking?

Prostate Cancer and Prostate Cancer and BMIBMI

Hsing, 2007

WHR and WHR and prostate cancerprostate cancer

Hsing, 2007

Metabolic Metabolic Syndrome Syndrome

and prostate and prostate cancercancer

Associations between obesity-Associations between obesity-related factors and prostate related factors and prostate

cancercancer

Prostate cancer and obesity, Prostate cancer and obesity, summarysummary

Overall, studies have not found a clear Overall, studies have not found a clear association between obesity and prostate association between obesity and prostate cancer.cancer.

Positive associations found with advance Positive associations found with advance disease and inverse associations found with disease and inverse associations found with localized disease.localized disease.

Potential mechanisms:Potential mechanisms: Hormones and obesityHormones and obesity

Associations between obese individuals and development Associations between obese individuals and development of undifferentiated tumors.of undifferentiated tumors.

IGF-1 pathwayIGF-1 pathway Delayed detection among obese individuals (lower Delayed detection among obese individuals (lower

PSA levels or difficulty in performing digital rectal PSA levels or difficulty in performing digital rectal exams)exams)

Different measures of Different measures of body weight change and body weight change and

cancercancer Weight differenceWeight difference BMI differenceBMI difference % change (weight or BMI)% change (weight or BMI)

[(measure at baseline minus measure at [(measure at baseline minus measure at age 21) / measure at age 21]×100 age 21) / measure at age 21]×100

% Average annual BMI change% Average annual BMI change % BMI change/(time between BMI % BMI change/(time between BMI

measures)measures)

Multiethnic Cohort StudyMultiethnic Cohort Study Cohort established to study diet and chronic disease endpoints Cohort established to study diet and chronic disease endpoints

in the US among a multiethnic populationin the US among a multiethnic population Consists of 215,251 adult men and women living in Hawaii and Consists of 215,251 adult men and women living in Hawaii and

in California.in California. African Americans (16.3%) African Americans (16.3%) Latino (22.0%)Latino (22.0%) Japanese American (26.4%)Japanese American (26.4%) Native Hawaiian (6.5%) Native Hawaiian (6.5%) White (22.9%) White (22.9%) Other (5.8%).Other (5.8%).

Recruited in 1993-1996, Ages 45-75Recruited in 1993-1996, Ages 45-75 Males: 96,810 and Females: 118,441Males: 96,810 and Females: 118,441

Epidemiology of Endometrial Epidemiology of Endometrial CancerCancer

The fourth most common The fourth most common cancer among US femalescancer among US females

42,160 estimated new 42,160 estimated new cases for 2009.cases for 2009.

Average 5 year survival Average 5 year survival rate:rate: 96% localized96% localized 68% regional68% regional 24% distant24% distant

White women have a White women have a higher incidence of higher incidence of endometrial cancer endometrial cancer compared to any other compared to any other ethnic group in the US.ethnic group in the US.

However, African-However, African-American women have a American women have a mortality rate 79% greater mortality rate 79% greater than that of Caucasian than that of Caucasian women.women.

Risk factorsRisk factors Estrogen-only therapy Estrogen-only therapy

in post-menopausal in post-menopausal womenwomen

ObesityObesity Late age at menopauseLate age at menopause Early age of menarcheEarly age of menarche Limited epidemiological Limited epidemiological

evidence for diabetes evidence for diabetes and hypertension. and hypertension.

Protective factorsProtective factors Use of oral Use of oral

contraceptivescontraceptives Increasing parityIncreasing parity SmokingSmoking

Follow-up and Exclusion Follow-up and Exclusion criteriacriteria

Follow-up:Follow-up: Follow-up time began at completion of baseline Follow-up time began at completion of baseline

question, and continued until:question, and continued until: Diagnosis of endometrial cancerDiagnosis of endometrial cancer Death, or Death, or End of follow-up (December 31, 2004)End of follow-up (December 31, 2004)

Incident endometrial cancer cases were identified by Incident endometrial cancer cases were identified by record linkage to the Hawaii Tumor Registry, the record linkage to the Hawaii Tumor Registry, the Cancer Surveillance Program for Los Angeles County, Cancer Surveillance Program for Los Angeles County, and the California State cancer registry.and the California State cancer registry.

Exclusion criteria: Exclusion criteria: Had a hysterectomyHad a hysterectomy Previous history cancer other than nonmelanoma skin cancerPrevious history cancer other than nonmelanoma skin cancer missing variables of wmissing variables of weight at baseline or age 21, height, age eight at baseline or age 21, height, age

at menarche, age at menopause, parity, oral contraceptive at menarche, age at menopause, parity, oral contraceptive use, postmenopausal hormone therapy, smoking status, use, postmenopausal hormone therapy, smoking status, physical activity, and educationphysical activity, and education

Epidemiological data and Epidemiological data and Statistical AnalysisStatistical Analysis

Measures of height and weight were self Measures of height and weight were self reported on baseline questionnairereported on baseline questionnaire

Cox proportional hazard models, age in days Cox proportional hazard models, age in days is the underlying time variableis the underlying time variable

In preliminary analysis, we also adjusted for In preliminary analysis, we also adjusted for calories and physical activity and observed calories and physical activity and observed no change in our findings. no change in our findings.

Final adjusted variables: education, body Final adjusted variables: education, body mass index, age at menarche, age at mass index, age at menarche, age at menopause, duration and type of hormone menopause, duration and type of hormone therapy, duration and oral contraceptive use, therapy, duration and oral contraceptive use, parity, smoking history, diabetes, parity, smoking history, diabetes, hypertension and BMI at age 21.hypertension and BMI at age 21.

SAS v 9.1 (Cary, NC)SAS v 9.1 (Cary, NC) STATA v10 (College Station, TX)STATA v10 (College Station, TX)

Measures in adulthood more predictive of endometrial cancer

weight

Weight is a confounder

Similar findings as weight

Ethnic differences Ethnic differences between BMI and body between BMI and body

fatfat


Example: Physical activity Example: Physical activity and endometrial cancerand endometrial cancer

No. CasesNo. Cases RRRR11 (95% CI) (95% CI) RRRR22 (95% CI) (95% CI) RRRR33 (95% CI) (95% CI)

Physical activity (METs)Physical activity (METs)33

Quartile 1: <1.4015Quartile 1: <1.4015 134134 1.001.00 1.001.00 1.001.00

Quartile 2: 1.4015 to Quartile 2: 1.4015 to <1.5900<1.5900

123123 0.86 (0.67,1.10)0.86 (0.67,1.10) 0.86 (0.67, 1.10)0.86 (0.67, 1.10) 0.89 (0.70, 1.14)0.89 (0.70, 1.14)

Quartile 3: 1.5900 to Quartile 3: 1.5900 to <1.7576<1.7576

116116 0.78 (0.61, 1.01)0.78 (0.61, 1.01) 0.81 (0.63, 1.05)0.81 (0.63, 1.05) 0.86 (0.67, 1.11)0.86 (0.67, 1.11)

Quartile 4: ≥ 1.7576Quartile 4: ≥ 1.7576 119119 0.81 (0.63, 1.04)0.81 (0.63, 1.04) 0.86 (0.67, 1.10)0.86 (0.67, 1.10) 0.92 (0.72, 1.19)0.92 (0.72, 1.19)

P P trendtrend 0.0720.072 0.1980.198 0.4930.49311 Age-adjusted RR. Age-adjusted RR. 22 RRs were adjusted for age, ethnicity, education, age at menarche, menopausal status, age at RRs were adjusted for age, ethnicity, education, age at menarche, menopausal status, age at menopause, duration and type of hormone therapy, oral contraceptive use, parity, smoking menopause, duration and type of hormone therapy, oral contraceptive use, parity, smoking history, diabetes, and hypertension. history, diabetes, and hypertension. 33 Additionally adjusted for BMI at baseline (quartiles). Additionally adjusted for BMI at baseline (quartiles).

BMI change and BMI change and endometrial cancerendometrial cancer

BMI at

Age 21 BMI at baseline

BMI change from age 21 to baseline

Endometrial Cancer

??

Confounding variables

r= 0.74

BMI change in Endometrial BMI change in Endometrial cancercancer

Body weightBody weightchange (%)change (%)

No. No. Cases Cases

RRRR11 (95% CI) (95% CI) RRRR2 2 (95% CI) (95% CI) RRRR3 3 (95% CI) (95% CI) RRRR44 (95% CI) (95% CI)

<-5<-5 2121 1.43 (0.82, 2.50)1.43 (0.82, 2.50) 1.37 (0.76, 2.46)1.37 (0.76, 2.46) 1.55 (0.87, 2.89)1.55 (0.87, 2.89) 1.48 (0.83, 2.68)1.48 (0.83, 2.68)

- 5 to <+5 - 5 to <+5 3030 1.001.00 1.001.00 1.001.00 1.001.00

5 to <155 to <15 8787 1.66 (1.09, 2.51)1.66 (1.09, 2.51) 1.83 (1.17, 2.99)1.83 (1.17, 2.99) 1.74 (1.12, 2.71)1.74 (1.12, 2.71) 1.79 (1.14, 2.79)1.79 (1.14, 2.79)

15 to <2515 to <25 8686 1.67 (1.10, 2.54)1.67 (1.10, 2.54) 1.92 (1.23, 2.99)1.92 (1.23, 2.99) 1.70 (1.08, 2.68)1.70 (1.08, 2.68) 1.81 (1.14, 2.86)1.81 (1.14, 2.86)

25 to <3525 to <35 7272 1.80 (1.17, 2.77)1.80 (1.17, 2.77) 2.09 (1.32, 3.31)2.09 (1.32, 3.31) 1.63 (1.00, 2.65)1.63 (1.00, 2.65) 1.80 (1.09, 2.98)1.80 (1.09, 2.98)

≥ ≥ 3535 196196 3.10 (2.08, 4.62)3.10 (2.08, 4.62) 4.12 (2.69, 6.30)4.12 (2.69, 6.30) 2.16 (1.34, 3.48)2.16 (1.34, 3.48) 2.60 (1.54, 4.39)2.60 (1.54, 4.39)

PP trend trend <0.001<0.001 <0.001<0.001 0.0440.044 0.0320.0321RRs were adjusted for age, ethnicity, education, age at menarche, age at menopause, duration and type of hormone therapy, oral contraceptive use, parity, smoking history, diabetes, and hypertension.2 Model 1 and adjusting for BMI at age 21 (quartiles)3 Model 1 and adjusting for BMI at baseline (WHO categories)3 Model 1 and adjusting for BMI at age 21 (quartiles) and BMI at baseline (WHO categories)

Conclusions for BMI change Conclusions for BMI change and endometrial cancerand endometrial cancer

Limitations of studyLimitations of study Self reported weightSelf reported weight

differential misclassification as a result of self-perceived differential misclassification as a result of self-perceived weightweight

Cannot account for weight fluctuationsCannot account for weight fluctuations Selection bias from differing response rates by ethnic Selection bias from differing response rates by ethnic

groupsgroups No measures of WHRNo measures of WHR

Strengths of studyStrengths of study Prospective study designProspective study design Ability to control for a variety of confounding variables in a Ability to control for a variety of confounding variables in a

multiethnic population.multiethnic population. ConclusionConclusion

Adult BMI gain is associated with increased risk in Adult BMI gain is associated with increased risk in endometrial cancerendometrial cancer

Risk may differ between ethnic groups, particular among Risk may differ between ethnic groups, particular among Japanese AmericansJapanese Americans

Postmenopausal hormone use and parity may modify the Postmenopausal hormone use and parity may modify the endometrial cancer risk associated with adult BMI gainendometrial cancer risk associated with adult BMI gain

The association between change in body The association between change in body mass index and upper aerodigestive tract mass index and upper aerodigestive tract cancers in the ARCAGE project: cancers in the ARCAGE project: multicenter case-control studymulticenter case-control study

Sungshim Lani ParkSungshim Lani Park1, 21, 2, Yuan-Chin Amy Lee, Yuan-Chin Amy Lee1, 21, 2, Manuela , Manuela MarronMarron22, Antonio Agudo, Antonio Agudo33, Wolfgang Ahrens, Wolfgang Ahrens44, Luigi Barzan, Luigi Barzan55, , Vladimir BenckoVladimir Bencko66, Simone Benhamou, Simone Benhamou7, 87, 8, Christine Bouchardy, Christine Bouchardy99, , Cristina CanovaCristina Canova1010, Xavier Castellsague, Xavier Castellsague33, David I Conway, David I Conway11, 1211, 12, , Claire M HealyClaire M Healy1313, Ivana Holcátová, Ivana Holcátová66, Kristina Kjaerheim, Kristina Kjaerheim1414, , Pagona LagiouPagona Lagiou1515, Raymond J Lowry, Raymond J Lowry1616, Tatiana V Macfarlane, Tatiana V Macfarlane1717, , Gary J MacfarlaneGary J Macfarlane1717, Bernard E McCartan, Bernard E McCartan1313, Patricia A , Patricia A McKinneyMcKinney11, 1811, 18, Franco Merletti, Franco Merletti1919, Hermann Pohlabeln, Hermann Pohlabeln44, Lorenzo , Lorenzo RichiardiRichiardi1919, Lorenzo Simonato, Lorenzo Simonato1010, Linda Sneddon, Linda Sneddon1616, Renato , Renato TalaminiTalamini2020, Dimitrios Trichopoulos, Dimitrios Trichopoulos2121, Ariana Znaor, Ariana Znaor2222, Paul , Paul BrennanBrennan22, Mia Hashibe, Mia Hashibe22

Manuscript under reviewManuscript under review

The association between change in body The association between change in body mass index and lung and upper aero-mass index and lung and upper aero-digestive tract cancersdigestive tract cancersSungshim Lani ParkSungshim Lani Park11, Yuan-Chin Amy Lee, Yuan-Chin Amy Lee11, Yan Cui, Yan Cui11, ,

Mia HashibeMia Hashibe22, Sander Greenland, Sander Greenland1,31,3, Hal , Hal MorgensternMorgenstern55, Donald P. Tashkin, Donald P. Tashkin66, Jenny T. Mao, Jenny T. Mao66, , Wendy CozenWendy Cozen66, Thomas M. Mack, Thomas M. Mack66, Zuo-Feng Zhang, Zuo-Feng Zhang1, 41, 4

Manuscript in preparationManuscript in preparation

Epidemiology of Upper Aerodigestive Epidemiology of Upper Aerodigestive tract (UADT) Cancerstract (UADT) Cancers

Sites: Oral cavity, pharynx, hypopharynx larynx, Sites: Oral cavity, pharynx, hypopharynx larynx, esophagusesophagus

Newly incident cases in the U.S.:Newly incident cases in the U.S.: Oral cavity and pharynx: 25,240 for males 10,480 for Oral cavity and pharynx: 25,240 for males 10,480 for

femalesfemales Larynx: 9,920 for males; 2370 for femalesLarynx: 9,920 for males; 2370 for females Esophagus (both SCC and Adenocarcinoma)12,940 for Esophagus (both SCC and Adenocarcinoma)12,940 for

males 3,530 for femalesmales 3,530 for females In the U.S. 5 year survival for oral cavity and pharynx.In the U.S. 5 year survival for oral cavity and pharynx.

82% localized82% localized 53% regional53% regional 28% distant28% distant

EU estimated 180,000 new cases per year, causes EU estimated 180,000 new cases per year, causes 110,000 deaths (Ferlay, 2004)110,000 deaths (Ferlay, 2004)

Major risk factors include tobacco smoking and alcohol Major risk factors include tobacco smoking and alcohol drinking, however at least 25% of cases are attributed to drinking, however at least 25% of cases are attributed to other factors, such as low SES, poor nutrition, HPV, and other factors, such as low SES, poor nutrition, HPV, and leanness. leanness. 1 Jemal A, et al., ACS Annual report, Cancer Statistics 2009.

Epidemiology of Lung Epidemiology of Lung CancerCancer Highest incidence secondary to prostate and Highest incidence secondary to prostate and

breast cancerbreast cancer 116,090 estimated new male cases for 2009116,090 estimated new male cases for 2009 103,350 estimated new female cases for 2009103,350 estimated new female cases for 2009

The highest mortality rate The highest mortality rate Estimated deaths for males: 88,900 Estimated deaths for males: 88,900 Estimated deaths for females: 70,490 Estimated deaths for females: 70,490

Poor 5-year survivalPoor 5-year survival 50% localized50% localized 21% regional21% regional 3% distant3% distant

1 Jemal A, et al., ACS Annual report, Cancer Statistics 2009.

Risk factors for lung and UADT Risk factors for lung and UADT cancerscancers

LungLung cancerscancers Tobacco smokingTobacco smoking GenderGender Passive smokePassive smoke Radon gasRadon gas Indoor air pollutionIndoor air pollution Poor dietPoor diet (Alcohol drinking) (Alcohol drinking) (HPV)(HPV) Leanness?Leanness?

UADT cancersUADT cancers Tobacco smokingTobacco smoking Alcohol drinkingAlcohol drinking Gender Gender Low SESLow SES HPVHPV Poor dietPoor diet Poor dentition Poor dentition Leanness?Leanness?

Prior Literature for UADT Prior Literature for UADT cancerscancersWeight measures from study entry

AuthorAuthor YearYear SiteSite GenderGender MeasureMeasure OR (95% CI)OR (95% CI)

KabatKabat 19941994 Oral and pharyngealOral and pharyngeal MenMen Lowest quartileLowest quartile 3.09 (2.12, 4.5)3.09 (2.12, 4.5)

WomenWomen Lowest quartileLowest quartile 1.84 (0.92, 3.69)1.84 (0.92, 3.69)

FranceschiFranceschi 20012001 Oral cavity and pharynxOral cavity and pharynx MenMen <22.7 kg/m<22.7 kg/m22 3.78 (2.52, 5.67)3.78 (2.52, 5.67)

WomenWomen <22.7 kg/m<22.7 kg/m22 1.99 (0.89, 4.44)1.99 (0.89, 4.44)

GaudetGaudet 20082008 HNCHNC BothBoth < 18.5 kg/m< 18.5 kg/m22 2.11 (1.70, 2.61)2.11 (1.70, 2.61)

GallusGallus 20032003 LaryngealLaryngeal WomenWomen >>26 kg/m26 kg/m22 0.4 (0.2, 1.1)0.4 (0.2, 1.1)

Earlier Weight measures

AuthorAuthor YearYear SiteSite GenderGender TimeTime MeasureMeasure OR (95% CI)OR (95% CI)

GaravelloGaravello 20062006 LaryngealLaryngeal BothBoth Age 30Age 30 Lowest quartileLowest quartile 1.13 (0.71, 1.81)1.13 (0.71, 1.81)

FranceschiFranceschi 20012001 Oral cavity and Oral cavity and pharynxpharynx

MenMen Age 30Age 30 <21.2 kg/m<21.2 kg/m22 2.15 (1.34, 3.45)2.15 (1.34, 3.45)

WomenWomen Age 30Age 30 <21.2 kg/m<21.2 kg/m22 1.21 (0.55, 2.64)1.21 (0.55, 2.64)

GaudetGaudet 20082008 HNCHNC BothBoth Age 20 to 30Age 20 to 30 < 18.5 kg/m< 18.5 kg/m22 0.90 (0.68, 1.19)0.90 (0.68, 1.19)

Rationale for associations Rationale for associations between leanness, UADT, between leanness, UADT,

and lung cancersand lung cancers Temporal ambiguityTemporal ambiguity Residual confoundingResidual confounding Biological mechanismBiological mechanism

leanness UADT cancer

Limitations of prior Limitations of prior literatureliterature

Does not explain whether observed Does not explain whether observed effect is due to leanness as a result effect is due to leanness as a result of weight change between these of weight change between these time points.time points.

Particularly since smoking and Particularly since smoking and alcohol drinking can affect body alcohol drinking can affect body weight.weight.

Alcohol-related cancer and Alcohol-related cancer and genetic susceptibility in Europe genetic susceptibility in Europe

(ARCAGE) study(ARCAGE) study Initialized by IARCInitialized by IARC Study designed to investigate and Study designed to investigate and

clarify the role of smoking, drinking, clarify the role of smoking, drinking, and genetic factors of UADT and genetic factors of UADT cancers.cancers.

14 centers and 10 European 14 centers and 10 European countriescountries

Recruitment between 2002-2005Recruitment between 2002-2005

Cases and ControlsCases and Controls 2,304 newly diagnosed cases (2,109 eligible 2,304 newly diagnosed cases (2,109 eligible

squamous cell carcinoma (SCC) and 195 eligible squamous cell carcinoma (SCC) and 195 eligible non-SCC cases)non-SCC cases)

Case eligibility: UADT cancer according to ICD-Case eligibility: UADT cancer according to ICD-O3.O3.

All ARCAGE centers used hospital-based All ARCAGE centers used hospital-based controls, except for UK center.controls, except for UK center.

2,227 controls, frequency matched to cases by 2,227 controls, frequency matched to cases by sex, age (5-year interval), and referral (or sex, age (5-year interval), and referral (or residence) area.residence) area.

Control eligibility include recent disease Control eligibility include recent disease diagnosis, not related to alcohol, tobacco, or diagnosis, not related to alcohol, tobacco, or dietary practices, and short hospital stay.dietary practices, and short hospital stay.

Epidemiological dataEpidemiological data Epidemiological data collection was performed Epidemiological data collection was performed

by identical interviewers using a lifestyle by identical interviewers using a lifestyle questionnairequestionnaire

3 measures of weight: time of recruitment, 2 3 measures of weight: time of recruitment, 2 years prior to recruitment, 30 years of age.years prior to recruitment, 30 years of age. Weight at study entry (interviewer measured)Weight at study entry (interviewer measured)

Not available at UK sitesNot available at UK sites Weights at 2 years prior and age 30 (self reported)Weights at 2 years prior and age 30 (self reported)

Not available for Paris siteNot available for Paris site

% BMI change = % BMI change =

(BMI at 2 years prior to study entry -BMI at (BMI at 2 years prior to study entry -BMI at age 30)/BMI at age 30 age 30)/BMI at age 30

Statistical AnalysesStatistical Analyses Excluded: Excluded:

195 non-SCC cases, due to limitation in 195 non-SCC cases, due to limitation in sample sizesample size

63 SCC cases and 54 controls for missing 63 SCC cases and 54 controls for missing data.data.

Adjustment variables: center, education, sex, Adjustment variables: center, education, sex, age, fruit and vegetable intake, tobacco age, fruit and vegetable intake, tobacco status/frequency, and alcohol frequency.status/frequency, and alcohol frequency.

Performed using SAS v9.1 (Cary, NC)Performed using SAS v9.1 (Cary, NC) Unconditional logistic regression model.Unconditional logistic regression model.

Table 1. Association between BMI, height, and BMI change and UADT SCCsTable 1. Association between BMI, height, and BMI change and UADT SCCs CaCa CoCo OR*OR* 95% CI95% CIBMI at study entry (kg/mBMI at study entry (kg/m22)**)**

13.0 to 18.4 13.0 to 18.4 139139 4646 1.901.90 (1.28, 2.82)(1.28, 2.82)18.5 to 24.9 18.5 to 24.9 915915 670670 1.001.0025.0 to 29.9 25.0 to 29.9 486486 768768 0.540.54 (0.46, 0.65)(0.46, 0.65)30.0 to 53.0 30.0 to 53.0 176176 277277 0.550.55 (0.43, 0.71)(0.43, 0.71)Missing Missing 1313 99PtrendPtrend <0.001<0.001

BMI at 2 years prior to interview (kg/mBMI at 2 years prior to interview (kg/m22)) ††

13.0 to 18.4 13.0 to 18.4 5757 2323 2.102.10 (1.16, 3.81)(1.16, 3.81)18.5 to 24.9 18.5 to 24.9 785785 688688 1.001.0025.0 to 29.9 25.0 to 29.9 613613 863863 0.740.74 (0.62, 0.88)(0.62, 0.88)30.0 to 53.0 30.0 to 53.0 252252 361361 0.740.74 (0.59, 0.93)(0.59, 0.93)Missing Missing 4242 2121PtrendPtrend <0.001<0.001

BMI at age 30 (kg/mBMI at age 30 (kg/m22)) ††

13.0 to 18.4 13.0 to 18.4 6161 5757 1.101.10 (0.72, 1.69)(0.72, 1.69)18.5 to 24.9 18.5 to 24.9 10661066 11881188 1.001.0025.0 to 29.9 25.0 to 29.9 401401 467467 1.021.02 (0.84, 1.22)(0.84, 1.22)30.0 to 53.0 30.0 to 53.0 116116 146146 0.940.94 (0.70, 1.27)(0.70, 1.27)Missing Missing 105105 9898PtrendPtrend 0.7210.721

Percent BMI change from age 30 to 2 years prior interviewPercent BMI change from age 30 to 2 years prior interview††

<−5% (BMI loss)<−5% (BMI loss) 280280 202202 1.151.15 (0.89, 1.49)(0.89, 1.49)−−5% to < +5% (stable)5% to < +5% (stable) 566566 501501 1.001.00≥ ≥ +5% (BMI gain)+5% (BMI gain) 788788 11541154 0.750.75 (0.62, 0.89)(0.62, 0.89)MissingMissing 115115 9999PtrendPtrend <0.001<0.001

*Adjusted for center, education, sex, age, fruit and vegetable intake, tobacco status/frequency, and alcohol frequency.** UK and Dublin centers not included in the model† Paris not included in the model.

Associations between BMI, BMI change and Associations between BMI, BMI change and UADT cancers, stratified by subsiteUADT cancers, stratified by subsite

Oral-oropharyngealOral-oropharyngeal Hypopharynx and larynxHypopharynx and larynx EsophagealEsophageal CaCa CoCo OR*OR* 95% CI95% CI CaCa CoCo OR*OR* 95% CI95% CI CaCa CoCo OR*OR* 95% CI95% CIBMI at study entry BMI at study entry

(kg/m(kg/m22)**)**13.0 to 18.4 13.0 to 18.4 7575 4646 2.112.11 (1.36, 3.28)(1.36, 3.28) 4646 4646 1.551.55 (0.91, 2.63)(0.91, 2.63) 1212 4646 5.435.43 (2.16, 13.64)(2.16, 13.64)18.5 to 24.9 18.5 to 24.9 430430 670670 1.001.00 390390 670670 1.001.00 6565 645645 1.001.0025.0 to 29.9 25.0 to 29.9 208208 768768 0.480.48 (0.39, 0.60)(0.39, 0.60) 225225 768768 0.600.60 (0.47, 0.76)(0.47, 0.76) 3737 751751 0.450.45 (0.28, 0.73)(0.28, 0.73)30.0 to 53.0 30.0 to 53.0 7575 277277 0.460.46 (0.33, 0.63)(0.33, 0.63) 8282 277277 0.620.62 (0.45, 0.86)(0.45, 0.86) 1212 273273 0.300.30 (0.15, 0.61)(0.15, 0.61)PtrendPtrend <0.001<0.001 <0.001<0.001 <0.001<0.001

BMI at 2 years prior to interview BMI at 2 years prior to interview (kg/m(kg/m22)) † †

13.0 to 18.4 13.0 to 18.4 3131 2323 2.042.04 (1.04, 3.99)(1.04, 3.99) 1212 2323 1.351.35 (0.52, 3.51)(0.52, 3.51) 1010 2121 4.954.95 (1.70, 14.46)(1.70, 14.46)18.5 to 24.9 18.5 to 24.9 395395 688688 1.001.00 305305 688688 1.001.00 5959 596596 1.001.0025.0 to 29.9 25.0 to 29.9 302302 863863 0.760.76 (0.62, 0.94)(0.62, 0.94) 240240 863863 0.660.66 (0.52, 0.83)(0.52, 0.83) 4949 768768 0.700.70 (0.45, 1.10)(0.45, 1.10)30.0 to 53.0 30.0 to 53.0 122122 361361 0.710.71 (0.54, 0.94)(0.54, 0.94) 9393 361361 0.620.62 (0.45, 0.84)(0.45, 0.84) 2626 323323 0.750.75 (0.43, 1.29)(0.43, 1.29)PtrendPtrend <0.001<0.001 <0.001<0.001 0.0180.018

BMI at age 30 (kg/mBMI at age 30 (kg/m22)) † †

13.0 to 18.4 13.0 to 18.4 3636 5757 1.181.18 (0.72, 1.94)(0.72, 1.94) 1919 5757 1.191.19 (0.63, 2.25)(0.63, 2.25) 44 5454 0.660.66 (0.21, 2.04)(0.21, 2.04)18.5 to 24.9 18.5 to 24.9 524524 11881188 1.001.00 398398 11881188 1.001.00 103103 10481048 1.001.0025.0 to 29.9 25.0 to 29.9 201201 467467 1.091.09 (0.87, 1.37)(0.87, 1.37) 152152 467467 0.940.94 (0.73, 1.21)(0.73, 1.21) 3333 412412 0.790.79 (0.49, 1.26)(0.49, 1.26)30.0 to 53.0 30.0 to 53.0 6262 146146 0.960.96 (0.67, 1.37)(0.67, 1.37) 4343 146146 0.980.98 (0.65, 1.48)(0.65, 1.48) 33 122122 0.230.23 (0.07, 0.77)(0.07, 0.77)PtrendPtrend 0.9690.969 0.6120.612 0.0370.037

Percent BMI change from age 30 to 2 years Percent BMI change from age 30 to 2 years prior to interviewprior to interview † †

<−5% (BMI loss)<−5% (BMI loss) 151151 202202 1.221.22 (0.90, 1.64)(0.90, 1.64) 9292 202202 0.870.87 (0.61, 1.24)(0.61, 1.24) 2424 177177 1.521.52 (0.81, 2.86)(0.81, 2.86)−−5% to < +5% 5% to < +5%

(stable)(stable) 286286 501501 1.001.00 223223 501501 1.001.00 4040 428428 1.001.00≥ ≥ +5% (BMI gain)+5% (BMI gain) 380380 11541154 0.710.71 (0.57, 0.88)(0.57, 0.88) 300300 11541154 0.660.66 (0.51, 0.84)(0.51, 0.84) 7979 10301030 0.840.84 (0.53, 1.33)(0.53, 1.33)PtrendPtrend 0.0020.002 0.0070.007 0.0510.051

*Adjusted for center, education, sex, age, fruit and vegetable intake, tobacco status/frequency, and alcohol frequency.

VariableVariable BMI change from age 30 to 2 years prior to study entryBMI change from age 30 to 2 years prior to study entry Loss (<-5%)Loss (<-5%) (−5% to < +5%) (−5% to < +5%) Gain (≥ +5%)Gain (≥ +5%) PtrendPtrendSmoking StatusSmoking StatusNever smokingNever smoking

cases/controlscases/controls 23/7123/71 36/17136/171 102/430102/430OR (95% CI)*OR (95% CI)* 1.231.23 (0.65, 2.33)(0.65, 2.33) 1.001.00 0.950.95 (0.60, 1.50)(0.60, 1.50) 0.3980.398

Former smokingFormer smokingcases/controlscases/controls 52/6752/67 93/16193/161 247/431247/431OR (95% CI)*OR (95% CI)* 1.191.19 (0.73, 1.94)(0.73, 1.94) 1.001.00 0.930.93 (0.67, 1.29)(0.67, 1.29) 0.2840.284

Current smokingCurrent smokingcases/controlscases/controls 205/64205/64 437/169437/169 439/293439/293OR (95% CI)*OR (95% CI)* 1.081.08 (0.75, 1.54)(0.75, 1.54) 1.001.00 0.590.59 (0.46, 0.76)(0.46, 0.76) <0.001<0.001

Drinking StatusDrinking StatusNever drinkingNever drinking


Former drinkingFormer drinkingcases/controlscases/controls 55/3255/32 89/3989/39 110/106110/106OR (95% CI)*OR (95% CI)* 0.830.83 (0.42, 1.65)(0.42, 1.65) 1.001.00 0.440.44 (0.25, 0.78)(0.25, 0.78) 0.0150.015

Current drinkingCurrent drinkingcases/controlscases/controls 211/129211/129 453/408453/408 624/914624/914OR (95% CI)*OR (95% CI)* 1.281.28 (0.95, 1.74)(0.95, 1.74) 1.001.00 0.790.79 (0.64, 0.96)(0.64, 0.96) <0.001<0.001

Associations between BMI change and UADT cancers, Associations between BMI change and UADT cancers, stratified by risk factorsstratified by risk factors


Associations between BMI change and UADT cancers, stratified by Associations between BMI change and UADT cancers, stratified by risk factors, con’t.risk factors, con’t.

Loss (<-5%)Loss (<-5%) (−5% to < +5%)(−5% to < +5%) Gain (≥ +5%)Gain (≥ +5%) PtrendPtrendSmoking and Drinking statusSmoking and Drinking statusNever smokes and drinksNever smokes and drinks


No drinking but smokesNo drinking but smokescases/controlscases/controls 8/188/18 15/1815/18 31/4431/44OR (95% CI)*OR (95% CI)* 0.300.30 (0.07, 1.21)(0.07, 1.21) 1.001.00 0.730.73 (0.25, 2.13)(0.25, 2.13) 0.2770.277

No smoking but drinksNo smoking but drinkscases/controlscases/controls 17/4817/48 27/13527/135 79/34079/340OR (95% CI)*OR (95% CI)* 1.281.28 (0.60, 2.76)(0.60, 2.76) 1.001.00 0.950.95 (0.56, 1.62)(0.56, 1.62) 0.4290.429

Smokes and drinksSmokes and drinkscases/controlscases/controls 249/113249/113 515/312515/312 655/680655/680OR (95% CI)*OR (95% CI)* 1.191.19 (0.89, 1.59)(0.89, 1.59) 1.001.00 0.630.63 (0.52, 0.77)(0.52, 0.77) <0.001<0.001

Fruit and Vegetable intakeFruit and Vegetable intake

Low fruits and vegetablesLow fruits and vegetablescases/controlscases/controls 171/70171/70 369/203369/203 442/477442/477OR (95% CI)*OR (95% CI)* 1.261.26 (0.86, 1.83)(0.86, 1.83) 0.630.63 (0.49, 0.81)(0.49, 0.81) <0.001<0.001

Medium fruit and vegetablesMedium fruit and vegetablescases/controlscases/controls 67/9067/90 138/178138/178 240/426240/426OR (95% CI)*OR (95% CI)* 0.760.76 (0.48, 1.20)(0.48, 1.20) 0.850.85 (0.56, 1.62)(0.56, 1.62) 0.9560.956

High fruit and vegetablesHigh fruit and vegetablescases/controlscases/controls 42/4242/42 59/12059/120 655/680655/680OR (95% CI)*OR (95% CI)* 2.062.06 (1.10, 3.86)(1.10, 3.86) 1.031.03 (0.64, 1.64)(0.64, 1.64) 0.0470.047


Loss (<-5%)Loss (<-5%) (−5% to < +5%) (−5% to < +5%) Gain (≥ +5%)Gain (≥ +5%) PtrendPtrendBMI at age 30BMI at age 30 <18.5kg/m<18.5kg/m22

cases/controlscases/controls 2/02/0 16/716/7 41/5041/50OR (95% CI)*OR (95% CI)* ---- 1.001.00 0.180.18 (0.02, 1.46)(0.02, 1.46) 0.0810.081

18.5kg/m18.5kg/m22 to <25 kg/m to <25 kg/m22

cases/controlscases/controls 120/62120/62 401/314401/314 538/810538/810OR (95% CI)*OR (95% CI)* 1.501.50 (1.00, 2.24)(1.00, 2.24) 1.001.00 0.720.72 (0.57, 0.90)(0.57, 0.90) <0.001<0.001

25kg/m25kg/m22 to <30 kg/m to <30 kg/m22


≥≥30kg/m30kg/m22


Time between age 30 and interviewTime between age 30 and interviewQuartile 1Quartile 1


Quartile 2Quartile 2cases/controlscases/controls 89/4289/42 176/139176/139 237/327237/327OR (95% CI)*OR (95% CI)* 1.681.68 (1.00, 2.81)(1.00, 2.81) 1.001.00 0.780.78 (0.56, 1.09)(0.56, 1.09) 0.0020.002

Quartile 3Quartile 3cases/controlscases/controls 68/4168/41 126/114126/114 222/313222/313OR (95% CI)*OR (95% CI)* 1.271.27 (0.72, 2.25)(0.72, 2.25) 1.001.00 0.790.79 (0.54, 1.15)(0.54, 1.15) 0.0470.047

Quartile 4Quartile 4cases/controlscases/controls 74/7874/78 99/11799/117 203/304203/304

OR (95% CI)*OR (95% CI)* 1.061.06 (0.65, 1.72)(0.65, 1.72) 1.001.00 0.900.90 (0.62, 1.31)(0.62, 1.31) 0.4280.428

Associations between BMI change and UADT cancers, stratified by risk factors, con’t.

Los Angeles Lung and UADT Los Angeles Lung and UADT cancer studycancer study

Population Based Case-Control StudyPopulation Based Case-Control Study 611 cases and 1040 controls611 cases and 1040 controls Newly diagnosed cases obtained using the rapid Newly diagnosed cases obtained using the rapid

ascertainment system of the Cancer Surveillance ascertainment system of the Cancer Surveillance Program for L.A. County, administered by the Program for L.A. County, administered by the Keck School of Medicine and Norris Keck School of Medicine and Norris Comprehensive Cancer Center (USC).Comprehensive Cancer Center (USC).

Controls were identified using a formal algorithm Controls were identified using a formal algorithm providing a list of households within the providing a list of households within the neighborhood of each individual case. neighborhood of each individual case.

Controls were matched to cases by age and Controls were matched to cases by age and gender.gender.

Study CriteriaStudy Criteria Subjects were residents of LA County at time of Subjects were residents of LA County at time of

recruitment (1999-2004).recruitment (1999-2004). During the study period were 18-65 years of age.During the study period were 18-65 years of age. Subjects were able to speak either English or Subjects were able to speak either English or

Spanish.Spanish.

Epidemiological data and Epidemiological data and statistical analysisstatistical analysisEpidemiological dataEpidemiological data

Epidemiological data collection was performed Epidemiological data collection was performed by identical interviewers using a lifestyle by identical interviewers using a lifestyle questionnairequestionnaire

2 measures of weight: 1 year prior to interview 2 measures of weight: 1 year prior to interview and weight at age 21. and weight at age 21.

% BMI change = (BMI at 2 years prior to study % BMI change = (BMI at 2 years prior to study entry - BMI at age 30)/ BMI at age 30entry - BMI at age 30)/ BMI at age 30

Statistical analysisStatistical analysis Analyzed using unconditional logistic Analyzed using unconditional logistic

regression.regression. Matching was broken allowing us to include Matching was broken allowing us to include

cases without match controls.cases without match controls. SAS v9.1SAS v9.1 Adjustment variables: gender, smoking status, Adjustment variables: gender, smoking status,

pack-years, education, race, calories, and age pack-years, education, race, calories, and age (and drinking for UADT cancers)(and drinking for UADT cancers)

Association between BMI, BMI change and UADT cancersAssociation between BMI, BMI change and UADT cancers

VariablesVariables Ca/CoCa/Co Crude OR (95% CI)Crude OR (95% CI) Adjust ORAdjust OR11(95% CI)(95% CI)BMI at age 21 BMI at age 21

<20.34<20.34 111/255111/255 1.001.00 1.001.0020.34 to <22.1520.34 to <22.15 108/260108/260 0.95 (0.70, 1.31)0.95 (0.70, 1.31) 0.94 (0.66, 1.35)0.94 (0.66, 1.35)22.15 to <24.3422.15 to <24.34 153/264153/264 1.33 (0.99, 1.80)1.33 (0.99, 1.80) 1.10 (0.77, 1.56)1.10 (0.77, 1.56)

≥≥24.3424.34 141/253141/253 1.28 (0.95, 1.73)1.28 (0.95, 1.73) 1.26 (0.88, 1.81)1.26 (0.88, 1.81)P P TrendTrend 0.0270.027 0.1270.127

BMI at 1 year priorBMI at 1 year prior<18.5 kg/m<18.5 kg/m22 13/1313/13 1.78 (0.81, 3.91)1.78 (0.81, 3.91) 1.79 (0.75, 4.25)1.79 (0.75, 4.25)18.5 to <2518.5 to <25 204/363204/363 1.001.00 1.001.0025 to <3025 to <30 199/401199/401 0.88 (0.69, 1.12)0.88 (0.69, 1.12) 0.84 (0.64, 1.11)0.84 (0.64, 1.11)

>>3030 109/260109/260 0.75 (0.56, 0.99)0.75 (0.56, 0.99) 0.73 (0.53, 1.00)0.73 (0.53, 1.00)P P TrendTrend 0.0130.013 0.0180.018

BMI change BMI change <−5% (weight loss)<−5% (weight loss) 51/3951/39 1.76 (1.08, 2.86)1.76 (1.08, 2.86) 1.29 (0.75, 2.21)1.29 (0.75, 2.21)

−−5% to <+5%5% to <+5% 107/144107/144 1.001.00 1.001.005% to <15%5% to <15% 114/256114/256 0.60 (0.43, 0.84)0.60 (0.43, 0.84) 0.66 (0.45, 0.95)0.66 (0.45, 0.95)15% to <25%15% to <25% 105/215105/215 0.66 (0.47, 0.93)0.66 (0.47, 0.93) 0.64 (0.43, 0.94)0.64 (0.43, 0.94)25% to <35%25% to <35% 51/15351/153 0.45 (0.30, 0.67)0.45 (0.30, 0.67) 0.41 (0.26, 0.65)0.41 (0.26, 0.65)

>>35%35% 85/224 85/224 0.51 (0.36, 0.73)0.51 (0.36, 0.73) 0.55 (0.37, 0.82)0.55 (0.37, 0.82)PP trend trend <0.001<0.001 <0.001<0.001

Average annual BMI Average annual BMI changechange

<0%<0% 69/5869/58 1.87 (1.22, 2.87)1.87 (1.22, 2.87) 1.46 (0.90, 2.36)1.46 (0.90, 2.36)0 to <0.25%0 to <0.25% 106/167106/167 1.001.00 1.001.00

0.25 to <0.5%0.25 to <0.5% 76 /17376 /173 0.69 (0.48, 1.00)0.69 (0.48, 1.00) 0.71 (0.47, 1.07)0.71 (0.47, 1.07)0.5 to <0.75%0.5 to <0.75% 82/16082/160 0.81 (0.56, 1.16)0.81 (0.56, 1.16) 0.79 (0.53, 1.19)0.79 (0.53, 1.19)0.75 to <1%0.75 to <1% 55/13555/135 0.64 (0.43, 0.95)0.64 (0.43, 0.95) 0.57 (0.36, 0.90)0.57 (0.36, 0.90)

≥ ≥ 1%1% 125/336125/336 0.59 (0.43, 0.81)0.59 (0.43, 0.81) 0.63 (0.44, 0.91)0.63 (0.44, 0.91)PP trend trend <0.001<0.001 <0.001<0.001Adjustment variables: gender, smoking status, pack-years, education, drinking, race, calories, and ageAdjustment variables: gender, smoking status, pack-years, education, drinking, race, calories, and age

Association between BMI, BMI change and UADT cancer Association between BMI, BMI change and UADT cancer stratified by genderstratified by genderMaleMale FemalesFemales

VariablesVariables Ca/CoCa/Co COR (95% CI)COR (95% CI) Adj ORAdj OR11 (95% (95% CI)CI)

Ca/CoCa/Co COR (95% CI)COR (95% CI) Adj ORAdj OR11 (95% (95% CI)CI)

BMI at age BMI at age 2121

<20.34<20.34 57/9657/96 1.001.00 1.001.00 54/15954/159 1.001.00 1.001.0020.34 to 20.34 to <22.15<22.15

69/14469/144 0.81 (0.52, 0.81 (0.52, 1.25)1.25)

1.06 (0.64, 1.06 (0.64, 1.75)1.75)

39/11639/116 0.99 (0.61, 0.99 (0.61, 1.59)1.59)

0.90 (0.53, 0.90 (0.53, 1.52)1.52)

22.15 to 22.15 to <24.34<24.34

132/180132/180 1.24 (0.83, 1.24 (0.83, 1.84)1.84)

1.41 (0.88, 1.41 (0.88, 2.24)2.24)

21/8421/84 0.74 (0.42, 0.74 (0.42, 1.30)1.30)

0.71 (0.38, 0.71 (0.38, 1.32)1.32)

≥≥24.3424.34 123/200123/200 1.04 (0.70, 1.04 (0.70, 1.54)1.54)

1.59 (1.00, 1.59 (1.00, 2.53)2.53)

18/5318/53 1.00 (0.54, 1.00 (0.54, 1.85)1.85)

0.85 (0.43, 0.85 (0.43, 1.71)1.71)

P P TrendTrend 0.3670.367 0.0170.017 0.6170.617 0.4820.482BMI at BMI at baselinebaseline

<18.5 kg/m<18.5 kg/m22 3/43/4 0.89 (0.20, 0.89 (0.20, 4.03)4.03)

1.21 (0.23, 1.21 (0.23, 6.30)6.30)

10/910/9 3.68 (1.43, 3.68 (1.43, 9.51)9.51)

2.53 (0.89, 2.53 (0.89, 7.21)7.21)

18.5 to <2518.5 to <25 147/174147/174 1.001.00 1.001.00 57/18957/189 1.001.00 1.001.0025 to <3025 to <30 158/296158/296 0.63 (0.47, 0.63 (0.47,

0.85)0.85)0.74 (0.53, 0.74 (0.53,

1.03)1.03)41/10541/105 1.29 (0.81, 1.29 (0.81,

2.07)2.07)1.14 (0.68, 1.14 (0.68,

1.92)1.92)>>3030 81/14981/149 0.64 (0.45, 0.64 (0.45,

0.91)0.91)0.71 (0.48, 0.71 (0.48,

1.06)1.06)28/11128/111 0.84 (0.50, 0.84 (0.50,

1.39)1.39)0.74 (0.42, 0.74 (0.42,

1.30)1.30)P P TrendTrend 0.0060.006 0.0620.062 0.1390.139 0.1230.123

BMI change BMI change <−5%<−5% 35/2435/24 1.57 (0.87, 1.57 (0.87,

2.85)2.85)1.26 (0.64, 1.26 (0.64,

2.47)2.47)16/1516/15 2.75 (1.14, 2.75 (1.14,

6.64)6.64)1.63 (0.63, 1.63 (0.63,

4.24)4.24)−−5% to <+5%5% to <+5% 88/9588/95 1.001.00 1.001.00 19/4919/49 1.001.00 1.001.005% to <15%5% to <15% 89/17689/176 0.55 (0.37, 0.55 (0.37,

0.80)0.80)0.64 (0.41, 0.64 (0.41,

0.98)0.98)25/8025/80 0.81 (0.40, 0.81 (0.40,

1.61)1.61)0.67 (0.32, 0.67 (0.32,

1.41)1.41)15% to <25%15% to <25% 78/14278/142 0.59 (0.40, 0.59 (0.40,

0.89)0.89)0.55 (0.35, 0.55 (0.35,

0.88)0.88)27/7327/73 0.95 (0.48, 0.95 (0.48,

1.90)1.90)0.86 (0.41, 0.86 (0.41,

1.80)1.80)25% to <35%25% to <35% 37/9237/92 0.43 (0.27, 0.43 (0.27,

0.70)0.70)0.38 (0.22, 0.38 (0.22,

0.65)0.65)14/6114/61 0.59 (0.27, 0.59 (0.27,

1.30)1.30)0.48 (0.20, 0.48 (0.20,

1.16)1.16)>>35%35% 54/9154/91 0.64 (0.41, 0.64 (0.41,

1.00)1.00)0.58 (0.35, 0.58 (0.35,

0.97)0.97)31/13331/133 0.60 (0.31, 0.60 (0.31,

1.16)1.16)0.52 (0.25, 0.52 (0.25,

1.09)1.09)PP trend trend .0005.0005 <0.001<0.001 .001.001 .004.004

Average annual BMI changeAverage annual BMI change<0%<0% 53/3153/31 2.51 (1.49, 2.51 (1.49,

4.24)4.24)2.04 (1.13, 2.04 (1.13,

3.69)3.69)16/2716/27 1.19 (0.53, 1.19 (0.53,

2.67)2.67)0.81 (0.33, 0.81 (0.33,

1.97)1.97)0 to <0.25%0 to <0.25% 85/12585/125 1.001.00 1.001.00 21/4221/42 1.001.00 1.001.00

0.25 to <0.5%0.25 to <0.5% 62/11462/114 0.80 (0.53, 0.80 (0.53, 1.21)1.21)

0.83 (0.52, 0.83 (0.52, 1.32)1.32)

14/5914/59 0.47 (0.22, 0.47 (0.22, 1.04)1.04)

0.39 (0.17, 0.39 (0.17, 0.91)0.91)

0.5 to <0.75%0.5 to <0.75% 56/10956/109 0.76 (0.49, 0.76 (0.49, 1.15)1.15)

0.71 (0.44, 0.71 (0.44, 1.16)1.16)

26/5126/51 1.02 (0.50, 1.02 (0.50, 2.06)2.06)

0.82 (0.38, 0.82 (0.38, 1.78)1.78)

0.75 to <1%0.75 to <1% 38/ 8438/ 84 0.67 (0.41, 0.67 (0.41, 1.07)1.07)

0.55 (0.32, 0.55 (0.32, 0.96)0.96)

17/5117/51 0.67 (0.31, 0.67 (0.31, 1.42)1.42)

0.51 (0.22, 0.51 (0.22, 1.18)1.18)

≥ ≥ 1%1% 87/15587/155 0.83 (0.56, 0.83 (0.56, 1.21)1.21)

0.79 (0.51, 0.79 (0.51, 1.23)1.23)

38/18138/181 0.42 (0.22, 0.42 (0.22, 0.79)0.79)

0.37 (0.18, 0.37 (0.18, 0.73)0.73)

PP trend trend <0.001<0.001 .003.003 0.0020.002 .008.008

Adjustment variables: gender, smoking status, pack-years, education, drinking, race, calories, and ageAdjustment variables: gender, smoking status, pack-years, education, drinking, race, calories, and age

LossLoss StableStable GainGain P trendP trendBMI at 21 Tertile 1BMI at 21 Tertile 1

case/controlscase/controls 8/18/1 29/3729/37 123/306123/306OR (95% CI)**OR (95% CI)** 7.22 (0.79, 65.74)7.22 (0.79, 65.74) 1.001.00 0.60 (0.31, 1.14)0.60 (0.31, 1.14) 0.0050.005

BMI at 21 Tertile 2BMI at 21 Tertile 2case/controlscase/controls 12/812/8 37/5137/51 114/289114/289OR (95% CI)**OR (95% CI)** 1.52 (0.49, 4.74)1.52 (0.49, 4.74) 1.001.00 0.47 (0.27, 0.80)0.47 (0.27, 0.80) <0.001<0.001

BMI at 21 Tertile 3BMI at 21 Tertile 3case/controlscase/controls 31/3031/30 41/5541/55 118/253118/253OR (95% CI)**OR (95% CI)** 1.10 (0.52, 2.32)1.10 (0.52, 2.32) 1.001.00 0.68 (0.40, 1.15)0.68 (0.40, 1.15) 0.0030.003

Never smokingNever smokingcase/controlscase/controls 14/1214/12 26/7226/72 118/403118/403OR (95% CI)**OR (95% CI)** 2.34 (0.90, 6.05 )2.34 (0.90, 6.05 ) 1.001.00 0.82 (0.49, 1.38)0.82 (0.49, 1.38) 0.0240.024

Former smokingFormer smokingcase/controlscase/controls 30/1530/15 51/4251/42 184/300184/300OR (95% CI)**OR (95% CI)** 1.53 (0.65, 3.58 )1.53 (0.65, 3.58 ) 1.001.00 0.56 (0.33, 0.94)0.56 (0.33, 0.94) 0.0010.001

Current smokingCurrent smokingcase/controlscase/controls 7/127/12 30/2930/29 53/14553/145OR (95% CI)**OR (95% CI)** 0.39 (0.11, 1.36 )0.39 (0.11, 1.36 ) 1.001.00 0.31 (0.15, 0.66)0.31 (0.15, 0.66) 0.0580.058

No DrinkingNo Drinkingcase/controlscase/controls 6/146/14 18/3418/34 75/21175/211OR (95% CI)**OR (95% CI)** 0.54 (0.15, 1.93)0.54 (0.15, 1.93) 1.001.00 0.64 (0.32, 1.28)0.64 (0.32, 1.28) 0.6220.622

Former DrinkersFormer Drinkerscase/controlscase/controls 28/1028/10 50/2650/26 188/161188/161OR (95% CI)**OR (95% CI)** 1.18 (0.46, 3.01)1.18 (0.46, 3.01) 1.001.00 0.75 (0.42, 1.34)0.75 (0.42, 1.34) 0.1690.169

Current DrinkersCurrent Drinkerscase/controlscase/controls 16/1516/15 39/8239/82 91/47491/474OR (95% CI)**OR (95% CI)** 2.19 (0.91, 5.31)2.19 (0.91, 5.31) 1.001.00 0.45 (0.27, 0.74)0.45 (0.27, 0.74) <0.001<0.001

Association of UADT cancer stratified by risk factors


Association of UADT cancer stratified by risk factors, Association of UADT cancer stratified by risk factors, contcontLossLoss StableStable GainGain P trendP trend

Fruit and Fruit and Vegetable Vegetable intakeintakecase/controlscase/controls 18/1018/10 31/4031/40 115/205115/205

OR (95% CI)**OR (95% CI)** 1.58 (0.55, 4.58)1.58 (0.55, 4.58)1.001.00 0.75 (0.39, 0.75 (0.39,

1.41)1.41)0.0920.092

Quartile 2Quartile 2case/controlscase/controls 7/57/5 26/3726/37 82/21682/216

OR (95% CI)**OR (95% CI)** 1.58 (0.38, 6.63)1.58 (0.38, 6.63)1.001.00 0.44 (0.22, 0.44 (0.22,

0.87)0.87)0.0040.004


OR (95% CI)**OR (95% CI)** 1.83 (0.57, 5.91)1.83 (0.57, 5.91)1.001.00 0.51 (0.27, 0.51 (0.27,

0.99)0.99)0.0040.004


OR (95% CI)**OR (95% CI)** 0.71 (0.25, 2.07)0.71 (0.25, 2.07)1.001.00 0.55 (0.28, 0.55 (0.28,

1.09)1.09)0.2000.200

TimeTimecase/controlscase/controls 12/1312/13 17/5217/52 80/17980/179

OR (95% CI)**OR (95% CI)** 2.61 (0.86, 7.88)2.61 (0.86, 7.88)1.001.00 0.32 (0.17, 0.32 (0.17,

0.63)0.63)0.8890.889


OR (95% CI)**OR (95% CI)** 0.46 (0.13, 1.62)0.46 (0.13, 1.62)1.001.00 0.36 (0.19, 0.36 (0.19,

0.68)0.68)0.0160.016


OR (95% CI)**OR (95% CI)** 1.69 (0.36, 7.84)1.69 (0.36, 7.84)1.001.00 0.79 (0.35, 0.79 (0.35,

1.75)1.75)0.2480.248


OR (95% CI)**OR (95% CI)** 1.54 (0.62, 3.87)1.54 (0.62, 3.87)1.001.00 0.41 (0.23, 0.41 (0.23,

0.73)0.73)<0.001<0.001


Prior studies investigating Prior studies investigating weight change and lung weight change and lung

cancerscancersAuthorAuthor yearyear journaljournal

study study designdesign studystudy

weight weight measuremeasure

differendifferencece RRRR LLLL ULUL

KabatKabat 20072007 epidemepidemiologyiology cohortcohort

Canadian Canadian National National Breast Breast Screening Screening StudyStudy

1 year 1 year priorprior

18 18 yearsyears

womenwomen 50 lbs+50 lbs+ 0.50.5 0.220.22 1.121.12

KabatKabat 20082008 AJEAJE cohortcohort WHIWHI baselinebaseline 18 18 yearsyears

women never women never smokerssmokers 30 lbs+30 lbs+ 0.760.76 0.450.45 1.31.3


women former women former smokerssmokers 30 lbs+30 lbs+ 0.760.76 0.560.56 1.031.03


women women currentcurrent 30 lbs+30 lbs+ 0.630.63 0.430.43 0.930.93

Association between anthropometric measures and lung cancerAssociation between anthropometric measures and lung cancerVariablesVariables Cases/ControlsCases/Controls Crude OR (95% CI)Crude OR (95% CI) Adjust ORAdjust OR11 (95% CI) (95% CI)BMI at age 21 BMI at age 21

<20.34<20.34 187/255187/255 1.001.00 1.001.0020.34 to <22.1520.34 to <22.15 148/259148/259 0.78 (0.59, 1.03)0.78 (0.59, 1.03) 0.96 (0.69, 1.35)0.96 (0.69, 1.35)22.15 to <24.3422.15 to <24.34 129/262129/262 0.67 (0.51, 0.89)0.67 (0.51, 0.89) 0.86 (0.60, 1.22)0.86 (0.60, 1.22)≥≥24.3424.34 134/248134/248 0.74 (0.56, 0.98)0.74 (0.56, 0.98) 0.90 (0.62, 1.30)0.90 (0.62, 1.30)P P TrendTrend 0.0160.016 0.4670.467

BMI at baselineBMI at baseline<18.5 kg/m<18.5 kg/m22 18/1318/13 1.89 (0.91, 3.94)1.89 (0.91, 3.94) 1.27 (0.52, 3.01)1.27 (0.52, 3.01)18.5 to <2518.5 to <25 263/360263/360 1.001.00 1.001.0025 to <3025 to <30 214/397214/397 0.74 (0.59, 0.93)0.74 (0.59, 0.93) 0.83 (0.62, 1.11)0.83 (0.62, 1.11)>>3030 114/257114/257 0.61 (0.46, 0.80)0.61 (0.46, 0.80) 0.55 (0.39, 0.77)0.55 (0.39, 0.77)P P TrendTrend <0.001<0.001 <0.001<0.001

BMI changeBMI change<−5% (weight loss)<−5% (weight loss) 51/3951/39 1.61 (0.99, 2.61)1.61 (0.99, 2.61) 0.99 (0.55, 1.80)0.99 (0.55, 1.80)−−5% to <+5%5% to <+5% 113/139113/139 1.001.00 1.001.005% to <15%5% to <15% 132/256132/256 0.63 (0.46, 0.88)0.63 (0.46, 0.88) 0.75 (0.50, 1.13)0.75 (0.50, 1.13)15% to <25%15% to <25% 113/214113/214 0.65 (0.46, 0.91)0.65 (0.46, 0.91) 0.70 (0.46, 1.06)0.70 (0.46, 1.06)25% to <35%25% to <35% 67/15367/153 0.54 (0.37, 0.79)0.54 (0.37, 0.79) 0.50 (0.31, 0.80)0.50 (0.31, 0.80)>>35%35% 122/222122/222 0.68 (0.48, 0.94)0.68 (0.48, 0.94) 0.50 (0.32, 0.76)0.50 (0.32, 0.76)PP trend trend <0.001<0.001 <0.001<0.001

Average annual weight changeAverage annual weight change<0%<0% 72/5872/58 1.73 (1.14 , 2.63)1.73 (1.14 , 2.63) 1.08 (0.64, 1.82)1.08 (0.64, 1.82)0 to <0.25%0 to <0.25% 119/166119/166 1.001.00 1.001.000.25 to <0.5%0.25 to <0.5% 108/173108/173 0.87 (0.62, 1.22)0.87 (0.62, 1.22) 0.81 (0.53, 1.22)0.81 (0.53, 1.22)0.5 to <0.75%0.5 to <0.75% 80/15980/159 0.70 (0.49, 1.00)0.70 (0.49, 1.00) 0.72 (0.46, 1.11)0.72 (0.46, 1.11)0.75 to <1%0.75 to <1% 67/13567/135 0.69 (0.48, 1.01)0.69 (0.48, 1.01) 0.67 (0.42, 1.07)0.67 (0.42, 1.07)≥ ≥ 1%1% 152/332152/332 0.64 (0.47, 0.87)0.64 (0.47, 0.87) 0.50 (0.34, 0.74)0.50 (0.34, 0.74)PP trend trend <0.001<0.001 <0.001<0.001

Adjustment variables: gender, smoking status, pack-years, education, race, calories, and ageAdjustment variables: gender, smoking status, pack-years, education, race, calories, and age

MaleMale FemalesFemalesVariablesVariables Ca/CoCa/Co ORc (95% CI)ORc (95% CI) Adj ORAdj OR11 (95% (95%

CI)CI)Ca/CoCa/Co ORc (95% CI)ORc (95% CI) Adj ORAdj OR11 (95% (95%

CI)CI)BMI at age 21 BMI at age 21

<20.34<20.34 48/9648/96 1.001.00 1.001.00 139/159139/159 1.001.00 1.001.0020.34 to 20.34 to <22.15<22.15

58/14458/144 0.81 (0.51, 0.81 (0.51, 1.28)1.28)

1.05 (0.59, 1.05 (0.59, 1.87)1.87)

90/11590/115 0.90 (0.63, 0.90 (0.63, 1.28)1.28)

1.01 (0.66, 1.01 (0.66, 1.54)1.54)

22.15 to 22.15 to <24.34<24.34

89/17989/179 0.99 (0.65, 0.99 (0.65, 1.53)1.53)

1.25 (0.73, 1.25 (0.73, 2.15)2.15)

40/8340/83 0.55 (0.35, 0.55 (0.35, 0.86)0.86)

0.57 (0.33, 0.57 (0.33, 0.96)0.96)

≥≥24.3424.34 101/195101/195 1.04 (0.68, 1.04 (0.68, 1.58)1.58)

1.31 (0.76, 1.31 (0.76, 2.25)2.25)

33/5333/53 0.71 (0.44, 0.71 (0.44, 1.16)1.16)

0.54 (0.30, 0.54 (0.30, 0.98)0.98)

P P TrendTrend 0.5020.502 0.2400.240 0.0210.021 0.0110.011BMI at baselineBMI at baseline

<18.5 kg/m<18.5 kg/m22 5/45/4 1.86 (0.49, 1.86 (0.49, 7.08)7.08)

1.95 (0.37, 1.95 (0.37, 10.2)10.2)

13/913/9 1.84 (0.76, 1.84 (0.76, 4.42)4.42)

1.10 (0.40, 1.10 (0.40, 3.05)3.05)

18.5 to <2518.5 to <25 116/173116/173 1.001.00 1.001.00 147/187147/187 1.001.00 1.001.0025 to <3025 to <30 122/292122/292 0.62 (0.45, 0.62 (0.45,

0.85)0.85)0.75 (0.51, 0.75 (0.51,

1.12)1.12)92/10592/105 1.11 (0.78, 1.11 (0.78,

1.59)1.59)0.88 (0.57, 0.88 (0.57,

1.34)1.34)>>3030 59/14759/147 0.60 (0.41, 0.60 (0.41,

0.88)0.88)0.62 (0.38, 0.62 (0.38,

1.01)1.01)55/11055/110 0.64 (0.43, 0.64 (0.43,

0.94)0.94)0.43 (0.26, 0.43 (0.26,

0.70)0.70)P P TrendTrend 0.0020.002 0.0290.029 0.0180.018 0.0010.001

BMI changeBMI change<−5%<−5% 30/2430/24 1.70 (0.91, 1.70 (0.91,

3.16)3.16)1.34 (0.60, 1.34 (0.60,

2.97)2.97)21/1521/15 1.46 (0.67, 1.46 (0.67,

3.17)3.17)0.84 (0.34 , 0.84 (0.34 ,

2.09)2.09)−−5% to <+5%5% to <+5% 67/9167/91 1.001.00 1.001.00 46/4846/48 1.001.00 1.001.00>>5%5% 199/499199/499 0.54 (0.38, 0.54 (0.38,

0.77)0.77)0.62 (0.39, 0.62 (0.39,

0.98)0.98)235/346235/346 0.71 (0.46, 0.71 (0.46,

1.10)1.10)0.63 (0.37, 0.63 (0.37,

1.08)1.08)PP trend trend <0.001<0.001 0.0120.012 0.0130.013 0.1380.138

Average annual weight changeAverage annual weight change<0%<0% 43/3143/31 2.53 (1.46, 2.53 (1.46,

4.38)4.38)1.94 (0.95, 1.94 (0.95,

3.96)3.96)29/2729/27 0.88 (0.46, 0.88 (0.46,

1.72)1.72)0.64 (0.29, 0.64 (0.29,

1.42)1.42)0 to <0.25%0 to <0.25% 68/12468/124 1.001.00 1.001.00 51/4251/42 1.001.00 1.001.000.25 to <0.5%0.25 to <0.5% 61/11461/114 0.98 (0.64, 0.98 (0.64,

1.50)1.50)0.97 (0.56, 0.97 (0.56,

1.66)1.66)47/5947/59 0.66 (0.37, 0.66 (0.37,

1.15)1.15)0.63 (0.33, 0.63 (0.33,

1.23)1.23)0.5 to <0.75%0.5 to <0.75% 39/109 39/109 0.65 (0.41, 0.65 (0.41,

1.04) 1.04) 0.75 (0.42, 0.75 (0.42,

1.34)1.34)41/5041/50 0.68 (0.38, 0.68 (0.38,

1.21) 1.21) 0.61 (0.30, 0.61 (0.30,

1.21)1.21)0.75 to <1%0.75 to <1% 35/8435/84 0.76 (0.46, 0.76 (0.46,

1.24)1.24)0.87 (0.47, 0.87 (0.47,

1.62)1.62)32/5132/51 0.52 (0.28, 0.52 (0.28,

0.94)0.94)0.46 (0.22, 0.46 (0.22,

0.95)0.95)≥ ≥ 1%1% 50/15250/152 0.60 (0.39, 0.60 (0.39,

0.93)0.93)0.63 (0.36, 0.63 (0.36,

1.10)1.10)102/180102/180 0.47 (0.29, 0.47 (0.29,

0.75)0.75)0.37 (0.21, 0.37 (0.21,

0.66)0.66)PP trend trend <0.001<0.001 0.0070.007 <0.001<0.001 0.0010.001

Table 2. Association between anthropometric measures and lung cancer, stratified by gender

Adjustment variables: smoking status, pack-years, education, race, calories, and ageAdjustment variables: smoking status, pack-years, education, race, calories, and age

NSCLCNSCLC SCLCSCLCVariablesVariables Ca/CoCa/Co Adjust ORAdjust OR11 (95% (95%

CI)CI)Ca/CoCa/Co Adjust ORAdjust OR11 (95% (95%

CI)CI)BMI at age 21 BMI at age 21

<20.34<20.34 162/255162/255 1.001.00 19/25519/255 1.001.0020.34, <22.1520.34, <22.15 121/259121/259 0.88 (0.62, 1.26)0.88 (0.62, 1.26) 18/25918/259 1.21 (0.54, 2.67)1.21 (0.54, 2.67)22.15, <24.3422.15, <24.34 110/262110/262 0.80 (0.55, 1.16)0.80 (0.55, 1.16) 13/26213/262 0.78 (0.32, 1.86)0.78 (0.32, 1.86)≥≥24.3424.34 106/248106/248 0.77 (0.52, 1.13)0.77 (0.52, 1.13) 22/24822/248 2.13 (0.96, 4.72)2.13 (0.96, 4.72)

P P TrendTrend 0.1510.151 0.1270.127BMI at baseline BMI at baseline

kg/mkg/m22

<18.5kg/m<18.5kg/m22 17/1317/13 1.37 (0.57, 3.30)1.37 (0.57, 3.30) 0/130/13 --18.5 to <2518.5 to <25 221/360221/360 1.001.00 33/36033/360 1.001.0025 to <3025 to <30 174/397174/397 0.78 (0.58, 1.06)0.78 (0.58, 1.06) 24/39724/397 0.58 (0.30, 1.13)0.58 (0.30, 1.13)>>3030 94/25794/257 0.53 (0.37, 0.76)0.53 (0.37, 0.76) 17/25717/257 0.55 (0.27, 1.14)0.55 (0.27, 1.14)

P P TrendTrend <0.001<0.001 0.1260.126BMI change BMI change

<−5% (weight <−5% (weight loss)loss)

46/3946/39 1.18 (0.64, 2.16)1.18 (0.64, 2.16) 4/394/39 0.27 (0.07, 1.09)0.27 (0.07, 1.09)

−−5% to <+5%5% to <+5% 93/13893/138 1.001.00 17/13917/139 1.001.005% to <25%5% to <25% 201/470201/470 0.71 (0.48, 1.04)0.71 (0.48, 1.04) 29/47029/470 0.47 (0.22, 1.00)0.47 (0.22, 1.00)>>25%25% 159/375159/375 0.53 (0.35, 0.79)0.53 (0.35, 0.79) 22/37522/375 0.21 (0.09, 0.49)0.21 (0.09, 0.49)

P P TrendTrend <0.001<0.001 0.0130.013Average annual weight Average annual weight

changechange<0%<0% 65/5865/58 1.27 (0.74, 2.16)1.27 (0.74, 2.16) 6/586/58 0.40 (0.12, 1.31)0.40 (0.12, 1.31)0 to <0.25%0 to <0.25% 96/16696/166 1.001.00 19/16619/166 1.001.000.25 to <0.5%0.25 to <0.5% 89/17389/173 0.83 (0.53, 1.28)0.83 (0.53, 1.28) 15/17315/173 0.67 (0.29, 1.52)0.67 (0.29, 1.52)0.5 to <0.75%0.5 to <0.75% 62/15962/159 0.67 (0.42, 1.06)0.67 (0.42, 1.06) 9/1599/159 0.46 (0.18, 1.20)0.46 (0.18, 1.20)0.75 to <1%0.75 to <1% 59/13559/135 0.76 (0.47, 1.23)0.76 (0.47, 1.23) 5/1355/135 0.22 (0.06, 0.72)0.22 (0.06, 0.72)≥ ≥ 1%1% 128/332128/332 0.55 (0.36, 0.82)0.55 (0.36, 0.82) 18/33218/332 0.26 (0.11, 0.61)0.26 (0.11, 0.61)

P P TrendTrend <0.001<0.001 0.0040.004

Association between anthropometric measures and lung cancer, stratified by subsite


Association between BMI change and lung cancer, stratified Association between BMI change and lung cancer, stratified by risk factorsby risk factors

<−5% <−5% (weight loss)(weight loss) −−5% to +5%5% to +5% 5% to <25%5% to <25% ≥≥25%25% PtrendPtrendBMI at age 21BMI at age 21Tertile 1Tertile 1

case/controlscase/controls 5/15/1 39/3639/36 90/13790/137 102/169102/169OR (95% CI)*OR (95% CI)* 2.22 (0.22, 22.89)2.22 (0.22, 22.89) 1.001.00 0.64 (0.33, 1.23)0.64 (0.33, 1.23) 0.42 (0.21, 0.81)0.42 (0.21, 0.81) 0.0020.002

Tertile 2Tertile 2case/controlscase/controls 21/821/8 32/5132/51 81/17481/174 53/11353/113OR (95% CI)*OR (95% CI)* 2.50 (0.85, 7.38)2.50 (0.85, 7.38) 1.001.00 0.87 (0.46, 1.64)0.87 (0.46, 1.64) 0.62 (0.31, 1.23)0.62 (0.31, 1.23) 0.0100.010

Tertile 3Tertile 3case/controlscase/controls 25/3025/30 42/5242/52 74/15974/159 34/9334/93OR (95% CI)*OR (95% CI)* 0.60 (0.25, 1.45)0.60 (0.25, 1.45) 1.001.00 0.64 (0.33, 1.23)0.64 (0.33, 1.23) 0.47 (0.22, 1.00)0.47 (0.22, 1.00) 0.2250.225

Never smokingNever smokingcase/controlscase/controls 4/124/12 10/7010/70 54/22454/224 37/17637/176OR (95% CI)*OR (95% CI)* 1.24 (0.28, 5.56)1.24 (0.28, 5.56) 1.001.00 1.32 (0.60, 2.90)1.32 (0.60, 2.90) 0.95 (0.41, 2.17)0.95 (0.41, 2.17) 0.5310.531

Former smokingFormer smokingcase/controlscase/controls 30/1530/15 63/4263/42 142/168142/168 120/132120/132OR (95% CI)*OR (95% CI)* 1.18 (0.48, 2.91)1.18 (0.48, 2.91) 1.001.00 0.82 (0.47, 1.42)0.82 (0.47, 1.42) 0.55 (0.31, 0.99)0.55 (0.31, 0.99) 0.0120.012

Current smokingCurrent smokingcase/controlscase/controls 17/1217/12 40/2740/27 49/7849/78 32/6732/67OR (95% CI)*OR (95% CI)* 0.62 (0.22, 1.74)0.62 (0.22, 1.74) 1.001.00 0.36 (0.17, 0.73)0.36 (0.17, 0.73) 0.23 (0.10, 0.50)0.23 (0.10, 0.50) <0.001<0.001


Association between BMI change and lung cancer, stratified by risk factors, Association between BMI change and lung cancer, stratified by risk factors, con’t.con’t.

<−5% (weight loss)<−5% (weight loss) −−5% to +5%5% to +5% 5% to <25%5% to <25% ≥≥25%25% PtrendPtrendFruit and Vegetable intakeFruit and Vegetable intakeQuartile 1Quartile 1

case/controlscase/controls 14/1014/10 49/3849/38 77/10977/109 66/9566/95OR (95% CI)*OR (95% CI)* 0.43 (0.14, 1.33)0.43 (0.14, 1.33) 1.001.00 0.68 (0.35, 1.32)0.68 (0.35, 1.32) 0.33 (0.16, 0.67)0.33 (0.16, 0.67) 0.0180.018

Quartile 2Quartile 2case/controlscase/controls 14/514/5 23/3623/36 58/12158/121 45/9345/93OR (95% CI)*OR (95% CI)* 2.87 (0.68, 12.17)2.87 (0.68, 12.17) 1.001.00 0.76 (0.34, 1.69)0.76 (0.34, 1.69) 0.54 (0.23, 1.28)0.54 (0.23, 1.28) 0.0110.011



Time to diseaseTime to diseasecase/controlscase/controls 6/136/13 17/4817/48 36/11036/110 22/6622/66OR (95% CI)*OR (95% CI)* 0.27 (0.06, 1.36)0.27 (0.06, 1.36) 1.001.00 0.73 (0.32, 1.63)0.73 (0.32, 1.63) 0.56 (0.22, 1.42)0.56 (0.22, 1.42) 0.8420.842

Quartile 2Quartile 2case/controlscase/controls 8/98/9 25/2925/29 66/12366/123 41/9841/98OR (95% CI)*OR (95% CI)* 0.52 (0.13, 2.08 )0.52 (0.13, 2.08 ) 1.001.00 0.55 (0.25, 1.21)0.55 (0.25, 1.21) 0.33 (0.14, 0.75)0.33 (0.14, 0.75) 0.0240.024



Adjustment variables: smoking status, pack-years, education, race, calories, and Adjustment variables: smoking status, pack-years, education, race, calories, and ageage

Discussion for associations Discussion for associations between BMI change and lung and between BMI change and lung and

UADT cancersUADT cancers BMI gain is inversely associated with UADT and lung BMI gain is inversely associated with UADT and lung

cancers cancers Potential reasons includePotential reasons include

Residual confoundingResidual confounding However, adjusted for other smoking and drinking However, adjusted for other smoking and drinking

variablesvariables Reverse causalityReverse causality Biological mechanism—Smoking/drinking, weight loss anti-Biological mechanism—Smoking/drinking, weight loss anti-

oxidative pathwayoxidative pathway 8-OHdG levels slightly higher in smokers than nonsmokers8-OHdG levels slightly higher in smokers than nonsmokers 8-OHdG levels increase per unit decrease in BMI (Mizoue, 8-OHdG levels increase per unit decrease in BMI (Mizoue,

2007)2007) Alcohol intake can induce free radical species in mice Alcohol intake can induce free radical species in mice

leukocytesleukocytes Low-BMI-high-waist circumference paradoxLow-BMI-high-waist circumference paradox

Observation that smokers and possibly alcohol drinkers, Observation that smokers and possibly alcohol drinkers, tend to have lower BMI but greater central adiposity.tend to have lower BMI but greater central adiposity.

Limitations, Strengths and Conclusions Limitations, Strengths and Conclusions regarding associations between lung, UADT regarding associations between lung, UADT cancers, and BMI changecancers, and BMI change LimitationsLimitations

Self-reported measures of weightSelf-reported measures of weight No WHRNo WHR Measure at 1 year prior to interview may not be early enough Measure at 1 year prior to interview may not be early enough

(LA study)(LA study) Use of semi-food frequency questionnaire limited the Use of semi-food frequency questionnaire limited the

possibility to account for energy balance (ARCAGE study)possibility to account for energy balance (ARCAGE study) StrengthsStrengths

Large sample sizes. Large sample sizes. Population based study design (LA study)Population based study design (LA study) The potential to adjust for a variety of smoking and drinking The potential to adjust for a variety of smoking and drinking

measures. measures. ConclusionsConclusions

BMI gain is inversely associated with lung and UADT cancers BMI gain is inversely associated with lung and UADT cancers Exact reasons for this associations remain unclear.Exact reasons for this associations remain unclear. BMI change may also serve as a potential indicator of early BMI change may also serve as a potential indicator of early

tumor development among a smoking and/or alcohol drinking tumor development among a smoking and/or alcohol drinking population.population.

Molecular approachMolecular approach Measure Measure

inflammatory inflammatory markersmarkers

Measure IGF1 Measure IGF1 and IGFBP3 levelsand IGFBP3 levels

Genotypes Genotypes sometimes sometimes correlates to correlates to phenotype (Cheng phenotype (Cheng I, 2007; Al-I, 2007; Al-Zahrani A, 2006)Zahrani A, 2006)

Calle EE, Kaaks R. Nature, 2004

Conclusions and Future Conclusions and Future directionsdirections The study of obesity is necessary in cancer.The study of obesity is necessary in cancer.

Measures of height and weight can be a valid, Measures of height and weight can be a valid, cost-effective means to measure adiposity.cost-effective means to measure adiposity.

As of now weight maintenance and physical As of now weight maintenance and physical activity is an effective means of prevention activity is an effective means of prevention against obesity related cancers.against obesity related cancers.

Investigating genetic and biologic Investigating genetic and biologic relationships between obesity and cancer relationships between obesity and cancer would be beneficial.would be beneficial.

Questionnaire design: ideal to have more than Questionnaire design: ideal to have more than 1 measure of adult weight1 measure of adult weight

One could also look into changes in adult One could also look into changes in adult height height

Measures of WHR would assist in Measures of WHR would assist in understanding the observed associations understanding the observed associations between BMI change and cancer.between BMI change and cancer.

A cost-effective, more precise method of A cost-effective, more precise method of measuring body adiposity is still needed.measuring body adiposity is still needed.

Thank you!Thank you!

Questions?Questions?

Obesity and Cancer S. Lani Park November 30, 2009.

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