www.worldcancercongress.org

Session code:

Cancer Atlas, 2nd edition

Major risk factors for cancer

CTS.4.230

Prof Paolo Vineis Imperial College London

Cancer as a multifactorial process The Hallmarks of Cancer From D Hanahan, The Lancet, February 8, 2014

Genes or environment?

Stomach cancer incidence in Hawaii Japanese and Caucasians by place of birth, 1973-77

Heredity Can Affect Many Types of Cancer Inherited Conditions That Increase Risk for Cancer (5-10% of cases)

Heritability of Colorectal Cancer

High Penetrance APC (FAP),

MMR (Lynch), TGFβR2,

POLD, SMAD4 (Familial

CRC)

Low Penetrance 8q23, 8q24, 10p14,

11q23, 14q22, 15q13, 18q21 (SMAD7), 19q31,

20p12, GSTM1 null, NAT2 G/G

Environment Genes

Familial Sporadic

Modifier Alleles

100—

80—

60—

40—

20—

0—

RA

TE

PE

R

10

0,0

00

Cancer can be caused by a variety of known risk factors, many of them preventable.

Dietary recommendations from the WCRF/AICR

The World Cancer Research Fund (WCRF/AICR) has released (and

periodically updates) guidelines for

cancer prevention: 1.

Be as lean as possible without becoming

underweight. 2.

Be physically active for at least 30 minutes every

day. 3.

Avoid sugary drinks. Limit consumption of energy-dense foods

(particularly processed foods high in added sugar, low in fiber, or high in fat).

4. Eat a variety of vegetables,

fruits, whole grains, and pulses

such as beans. 5.

Limit consumption of red meats (such as beef, pork

and lamb) and avoid processed meats.

6. Limit alcoholic drinks to 2 drinks per day for

men and 1 drink per day for women.

7. Limit consumption of salty foods and foods processed

with salt (sodium). 8.

Don’t use supplements to protect against cancer. Instead, choose a

balanced diet with a variety of foods.

Northern America

Latin America & the Caribbean

Africa

9% Asia

Europe 5%

14%

21% 16%

4

Compared with Northern America, the estimated prevalence of human papillomavirus (HPV), the leading cause of cervical cancer, is about three times as high in Europe

and Latin America, and four times as high in Africa.

ESTIMATED HPV PREVALENCE (%), ALL TYPES COMBINED, AMONG WOMEN BY REGION, 1995-2009

0.7% General

male populatio

n

13% Benzidine

manufacture

23% Mixed exposure to carcinogenic

amines

43% Exposure to

beta-naphthylamine

100% Distillers of

beta-naphthylamine

0

10

20

30

40

50

60

70

80

90

100

3

Increasing intensity of occupational exposure to carcinogens carries

increasing risk of developing cancer.

5

Smoking is associated with at least 16 types of cancers.

Nasal cavity and

paranasal sinus Oral

cavity Pharynx

Larynx

Esophagus

Bone marrow (acute

myeloid leukemia)

Lungs

Liver

Stomach Pancreas

Kidneys

Ureter

Colorectum

Urinary bladder

1

Cancer is more often caused by the environment a person lives in, rather

than his or her innate biology.

CANCER INCIDENCE AGE-STANDARDIZED RATES (WORLD) PER 100,000, CIRCA 1970

Colon Cancer

Stomach Cancer

22.4 23.9

6.3 Japanese in Japan

91.4

34.9

17.4

Hawaii Japanese Whites in Hawaii

Rates in Japanese

Hawaiians are

more similar to cancer rates of

white

Hawaiians,

rather than Japanese in Japan.

Ovaries Cervix

2

18

19

Human papillomavirus types 16 and 18 are the most prevalent types of HPV worldwide,

accounting for over 70% of all cervical cancer cases.

Cancer sites for which there is “sufficient” evidence of carcinogenicity of tobacco smoking according to the IARC Working Group: number of studies on which the evaluation was based and average relative risk. CC=case-control Cancer site Number of studies RR

CC Cohort Lung >100 37 15-30 Urinary tract 50 24 3 Upper aero-digestive tract: Oral cavity, Oro-and hypopharynx 28 6 4-5 Oesophagus 45 19 1.5-5 Larynx 25 5 10 Pancreas 38 27 2-4 Stomach 44 27 1.5-2 Liver 29 29 1.5-2.5 Kidney 13 8 1.5-2.0 Uterine cervix 49 14 1.5-2.5

(Vineis et al, JNCI 2004 Jan 21;96(2):99-106)

Tobacco Use and Cancer Tobacco Use and Cancer

Trends in Overweight and Obesity

WHO, 2010

Colorectal cancer and dietary fibre

Statistical model adjusted for : energy, height, weight, physical activity, alcohol and tobacco

0.2

0.4

0.6

0.8

1.0

10.0 15.0 20.0 25.0 30.0 35.0 40.0

fibre (g/day)

RR es

timate

correctedupper limit

corrected

correctedlower limit

S. Bingham et al. , The Lancet, May 21, 2003

Bacterial metabolism in colon!Bacterial mass!

Apopotosis?!Reduced transit

time, dilution,less !mucosal contact!

SCFA!Butyrate!Lower pH!

Physical activity level around the world

Source: WHO

Cancer Research Fund) RECOMMENDATIONS Fund) RECOMMENDATIONS Be as lean as possible within the normal range of body weight

Be as lean as possible within the normal range of body weight

Be physically active as part of everyday life Be physically active as part of everyday life

Limit consumption of energy-dense foods Avoid sugary drinks Limit consumption of energy-dense foods Avoid sugary drinks

Eat mostly foods of plant origin Eat mostly foods of plant origin

Limit intake of red meat and avoid processed meat Limit intake of red meat and avoid processed meat

Limit alcoholic drinks Limit alcoholic drinks

Limit consumption of salt Avoid mouldy cereals (grains) or pulses (legumes)

Avoid mouldy cereals (grains) or pulses (legumes) Aim to meet nutritional needs through diet alone

Aim to meet nutritional needs through diet alone

Mothers to breastfeed; children to be breastfed Mothers to breastfeed; children to be breastfed

Follow the recommendations for cancer prevention Follow the recommendations for cancer prevention

Infectious Agents and Cancer

agents worldwide •  25% in Africa •  <10% in Europe (1 in 33 in UK) •  <10% in Europe (1 in 33 in UK)

Agent Cancer

HPV (16,18) Cervix, Head and Neck

EBV Hodgkin’s Lymphoma, Burkitts

HCV, HBV Liver

H. Pylori Stomach

Occupational Carcinogens

Some Carcinogens in the Workplace

Mesothelioma deaths by sex and year in England and Wales. From Hodgson et al, 2005

Parkin’s estimate of preventable cancers (Parkin et al, 2012) => 5 servings of fruit and vegetables; =>23 g/day of fibers; <=6 g/day of salt; BMI<=25 kgm-2; physical activity=> 30 min 5 times/week; breastfeeding at least 6 months 14 risk factors and 18 cancer sites have been considered. The result is that 45% of cancers in men and 40% in women could have been prevented had risk factors been reduced to the optimal levels or eliminated (like tobacco). Reduction/elimination of the same risk factors would lead to a substantial reduction also of cases of cardiovascular disease, renal disease, hepatic disease, diabetes and possibly some neurological diseases.

Advantages of primary prevention (P Vineis, C Wild. Global cancer patterns: causes and prevention.The Lancet 2014 Feb 8;383(9916):549-57)

Primary prevention decreases social inequalities, when it is effective. Current structural reforms increase inequalities within/between countries Primary preventive activities have an impact that go beyond those who are directly affected by it, for example for an indirect effect. The typical instance is herd immunity. Similarly, banning smoking in public places has a positive effect not only in those potentially exposed to secondhand smoke (the target population), but also in smokers, who will smoke less. Prevention is usually effective on more than one disease (cancer CVD, diabetes, hypertension, neurological diseases) and does not require to be renewed at each generation like therapies.

Threats to primary prevention Primary prevention acts on exposures to risk factors. An exclusively individualized approach is unlikely to have a strong impact, while societal actions are more likely to be effective. However, the tendency to reduce public expenditure and privatize parts of the health care systems will impact on preventive activities such as health promotion, which are not appealing for private enterprises. In the US, Europe and Canada less than 4% of the current public budget is spent in cancer prevention (including all types)(Sullivan et al, 2012)

The spread of the cancer epidemic to low-income countries should and could be stopped now. Thank you