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Epidemiology of pancreatic
cancer- setting the scene
Linda Sharp
National Cancer Registry, Cork
021 470 3926
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Introduction
• Descriptive epidemiology o incidence, mortality - worldwide and in Ireland
o treatment and survival in Ireland
• Aetiology of pancreatic cancer
o established risk factorso recent hypotheses
• PanCAM study o All-Ireland case-control study of pancreatic cancer
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Pancreatic cancer worldwideIncidence
• ~232,000 new cases diagnosed worldwide each year• 61% occur in developed countries
• ranks 13th in terms of most common cancers
Mortality • ~227,000 deaths from pancreatic cancer worldwide each year• ranks 8th in terms of most common causes of cancer death
• Mortality/incidence ratio (M/I) = 98%
Parkin DM et al., CA – Cancer J Clin 2005; 55: 74-108
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Incidence in Ireland
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Pancreatic cancer incidence in
Ireland• 360 new cases diagnosed each year (1994-2005)
• 179 in males; 181 in females
• accounts for 2.5% of cancers in males, 2.7% in females*
• 10th most common cause of cancer in both sexes*
* excluding non-melanoma skin cancer
Source: National Cancer Registry, 2007
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Age composition of pancreatic cancer cases at
diagnosis, by sex, Ireland 2003-2005
25.9%
17.3%
4.4%
52.4%
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Rising numbers of cases over time, Ireland
1891852003-2005
+12%+14%% change over time
• Increase mainly due to demographic changes
1701621994-1996
FemalesMales Average annual numbers of cases
by period of diagnosis
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Age-standardised incidence rates of pancreatic by
year of diagnosis and sex, Ireland, 1994-2005
0
1
2
3
4
5
6
7
8
9
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year of diagnosis
W A S R p e r 1
0 0 , 0 0 0
Males
Females
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Age-standardised incidence of pancreatic cancer, bycountry/region, 2002
0 1 2 3 4 5 6 7 8 9 10
Poland
Japan
Italy
USA
Denmark
Finland
Russia
Norway
Germany
France
UK
Australia
Ireland
Spain
Netherlands
South America
Central America
China
Kuwait
Turkey
South Africa
Egypt
India
Uganda
WASR per 100,000
Males
Females
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Future incidence in Ireland
• Incidence projected to rise in future years
National Cancer Registry, 2006
1891852003-2005
+71%+110%% change between 2003-05 and 2020
3243882020
1701621994-1996
FemalesMales Average annual numbers of casesby period of diagnosis
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Mortality in Ireland
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Pancreatic cancer mortality in
Ireland• 367 deaths each year (1994-2004)
• 185 in males; 182 in females
• Accounts for 4.6% of cancer deaths in males, 5.2% infemales
• 8th most common cause of cancer death in males, 6thin females
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Age-standardised mortality rates of pancreatic by
year and sex, Ireland, 1950-2004
0
1
2
3
4
5
6
7
8
9
10
1 9 5 0
1 9 5 3
1 9 5 6
1 9 5 9
1 9 6 2
1 9 6 5
1 9 6 8
1 9 7 1
1 9 7 4
1 9 7 7
1 9 8 0
1 9 8 3
1 9 8 6
1 9 8 9
1 9 9 2
1 9 9 5
1 9 9 8
2 0 0 1
2 0 0 4
Year of death
W A S R p e
r 1 0 0 , 0 0 0
Males
Females
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Treatment and survival
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Treatment received, Ireland, 1994-2003
7.4%232Radiotherapy 45.7%1,447Other surgical treatment***
41.9%1,327No treatment
* categories not exclusive ** resection: radical pancreaticoduodenectomy, partial or total pancreatectomy
** stents, biliary bypass, etc
12.3%389Chemotherapy
7.2%229Cancer-directed surgery**
% No.Treatment received within 1-year of
diagnosis*
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Treatment received: Ireland, all patients
0
5
10
1520
25
1 9 9 4
1 9 9 5
1 9 9 6
1 9 9 7
1 9 9 8
1 9 9 9
2 0 0 0
2 0 0 1
2 0 0 2
2 0 0 3
year of diagnosis
% o f
c a s e s r e c e i v i n g t
chemotherapy radiotherapy
surgery (resection)
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0
10
20
30
40
50
1 9 9 4
1 9 9 5
1 9 9 6
1 9 9 7
1 9 9 8
1 9 9 9
2 0 0 0
2 0 0 1
2 0 0 2
2 0 0 3
year of diagnosis
%
o f c a s e s
r e c e i v i n g c h
e m o
resected not resected
Chemotherapy receipt: by resection
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Survival, Ireland, 1994-2003
• median FU = 2.7 months
• 1-year (crude) survival = 13.7%
o 49.6% in surgically treated patients
o 10.9% in non-surgical patients
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Survival, Ireland, 1994-2003
• median FU = 2.7 months
• 1-year (crude) survival = 13.7%
o 49.6% in surgically treated patients
o 10.9% in non-surgical patients
• Improvement in survival over time
11.5%10.3%non-surgical
61.5%39.5%surgically treated
14.7%12.5%all patients
diagnosed 1999-03diagnosed 1994-981-year survival
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Aetiology –
pancreatic cancer risk factors
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Aetiology
• Relatively little known about risk factors
• Relatively few studieso difficult to conduct
• poor patient prognosis
• low participation rates• proxy interviews – inaccurate data
• Growing interest in recent yearso several new studies starting o consortia forming of (high quality) existing studies and new
studies
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Medical history
Chronic pancreatitis (CP)
• CP patients have ~18-fold higher risk of pancreatic cancer thangeneral population (Lowenfels et al., 1999; Talamini et al., 1999;
Malka et al., 2002)
• prolonged inflammation may initiate or promote development ofcancer
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Medical history Chronic pancreatitis (CP)
• CP patients have ~18-fold higher risk of pancreatic cancer than generalpopulation (Lowenfels et al., 1999; Talamini et al., 1999; Malka et al., 2002)
• prolonged inflammation may initiate or promote development of cancer
Diabetes
• positive association between prior diabetes and pancreatic cancer
2.0 (1.37-3.01) Type I or young
onset
3 cohort; 6 case-controlStevens et al.,
2007
1.5 (1.3-1.8) Type II9200Huxley et al.,
2005
Pooled Relative Risk
(RR)
with 95% CI
DiabetesNo. of
patients/studies
Reference
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AllergiesHistory of atopy-related allergies
• Associated with reduced risk of pancreatic cancer (Gandini et al., 2005)
o respiratory allergy (excl asthma): pooled RR=0.63 (0.52-0.76)
o dermal allergy: pooled RR=0.66 (0.49-08.89)
History of asthma
• Unrelated to pancreatic cancer risk: pooled RR=1.01 (0.77-1.31)
History of food or drug allergies
• Unrelated to pancreatic cancer risk: pooled RR=1.08 (0.70-1.58)
Postulated mechanism
• hyperactive immune system leading to increased immune surveillance
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Dental health
• Possible positive association with tooth loss and/or peridontaldisease
Possible mechanism: inflammation
1.64 (1.19-2.26)
History ofperidontal
disease vs none
cohort; male healthprofessionals; USA
Michaud et al.,2007
1.63 (1.09-2.46)
Toothless vs lost0-10 teeth
cohort; male smokers;Finland
Stolzenberg-Solomon et al.,2003
RR with 95% CI
ComparisonStudy design, etcReference
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Smoking
“Cancer of the pancreas is causally associated with cigarette
smoking “
(International Agency for Research on Cancer, 2004)
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Smoking
“Cancer of the pancreas is causally associated with cigarette
smoking “
(International Agency for Research on Cancer, 2004)
• Smokers vs non-smokers: RR = 1.5-3.0
• Risk increases with
o duration of smoking
o number of cigarettes smoked daily
• Risk decreases with increasing time since quitting smoking
• Stronger risks with smoking in more recent years – smoking plays role in later
stages of pancreatic carcinogenesis ?
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Body mass index
There is convincing evidence that greater body fatness is a
cause of pancreatic cancer
(WCRF/AICR, 2007)
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Body mass index
There is convincing evidence that greater body fatness is acause of pancreatic cancer
(WCRF/AICR, 2007)
• 13 of 23 cohort studies found increased risk with increased body fatness/BMI
o pooled RR = 1.14 (1.07-1.22) per increase of 5 kg/m2
o dose-response relationship (↑ risk with ↑ BMI)
• Possible mechanismso inflammation
o effects on steroid hormones and growth factors
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Body fat distribution/central adiposity
• Apple-type fat distribution (central adiposity/abdominal fatness) is
a probable cause of pancreatic cancer (WCRF/AICR, 2007)
↑ risk with ↑ratio2 Waist-hip ratio
↑ risk 1 Tendency for
central weight gain
↑ risk with ↑circumference
3 Waistcircumference
FindingsNo. of cohort
studies
Measure
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Physical activity There is limited evidence that greater physical activity protects
against pancreatic cancer
(WCRF/AICR, 2007)
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Physical activity There is limited evidence that greater physical activity protects
against pancreatic cancer
(WCRF/AICR, 2007)
3/4 cohort Walking
Studies reporting ↓ risk with ↑activity
5/9 cohort; 3/3 case-controlRecreational activity
1/1 cohort; 2/2 case-controlOccupational activity
3/5 cohort; 1/1 case-control Vigorous activity
2/3 cohort; 1/1 case-control Total activity
No. of positive studiesMeasure
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Folate
• B vitamin
• natural sources – green leafy vegetables,
liver, yeast, meat, milk, tea
• synthetic form – folic acid
• key role in DNA methylation and DNAsynthesis and repair
• folate/folic acid may be involved in arange of diseases including cancers
R l i i k (RR) i h 95% CI f hi h
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Relative risk (RR), with 95% CI, for highest vs
lowest folate intake
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Baghurst et
al., 1991:
M+F
Silverman et
al., 1998: M
Silverman et
al., 1998: F
Stolzenberg-
Solomon et
al., 2001: M
Skinner et al.,
2004: M
Skinner et al,
2004: F
Larsson et
al., 2006:
M+F
R R
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Other dietary risk factors
Fruit
• Possible inverse association (WCRF/AICR, 2007)
0.89 (95% CI 0.95-0.98)8case-control
0.92 (95% CI 0.81-1.04)3cohort
Relative risk (RR) per 100/g day No. of studiesStudy type
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Other dietary risk factors
Fruit
• Possible inverse association (WCRF/AICR, 2007)
0.89 (95% CI 0.95-0.98)8case-control
0.92 (95% CI 0.81-1.04)3cohort
Relative risk (RR) per 100/g day No. of studiesStudy type
Red meat
• Possible positive association (WCRF/AICR, 2007)
• 4 / 7 cohort studies found increased risk in highest vs lowestintake groups
• RRs in range 1.5-2.8
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Genetic contribution to pancreatic cancer
• 5-10% of pancreatic cancers caused by an inherited disorder (Lynch et
al., 1996)
o hereditary pancreatitis
o familial breast cancer (BRCA2)
o HNPCC, FAP
o familial atypical multiple mole melanoma (FAMMM)
• Evidence for genetic contribution to pancreatic cancer over and above
what can be explained by familial syndromes
o 3-5-fold higher risk of pancreatic cancer in those with a closerelative with the disease (Michaud, 2004).
o not explained by familial clustering of environmental or lifestyle
factors
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What other genes could be involved?
Low penetrance, polymorphic genes acting together with othergenes, or environmental or lifestyle exposure(s), to affect risk of
pancreatic cancer
gene-gene or gene-environment interaction
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What other genes could be involved?
Low penetrance, polymorphic genes acting together with othergenes, or environmental or lifestyle exposure(s), to affect risk of
pancreatic cancer
gene-gene or gene-environment interaction
Examples MTHFR, MTR, TS related to folate
CYP1A2 tobacco
NAT1, NAT2 tobacco, red meat
XRCC1, XPC DNA repair capacity
(Wang et al., 2005; Jiao et al., 2006; Li et al., 2006; Wang et al., 2006)
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Pancreatic Conditions Aetiology and
Management:an all-Ireland case-control study
P CAM ll I l d l d
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PanCAM: an all-Ireland case-control study
Aim
To establish a data and specimen bank for studies into aetiology, early diagnosis, andsurvival of pancreatic cancer in Ireland
Objectives
• To investigate
o risk factors for pancreatic cancer
• diet, lifestyle, medical history, medication use, occupational exposures, etco patterns of referral, treatment, patient quality of life (QoL) and survival
o burden on carers
o To establish a network of clinicians, other health professionals and researchers
interested in pancreatic cancer in Ireland ( All-Ireland Pancreatic Cancer Study Group)
P CAM ll I l d t l t d
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PanCAM: an all-Ireland case-control study
Subjects
Cases: newly diagnosed with pancreatic cancer; autumn 2007 onwardsControls: individuals without pancreatic cancer; from general practices(Carers: main family member involved in caring for patient)
Participation
Cases and controls: socio-demographic, lifestyle and dietary questionnaire
blood (serum, plasma, DNA); urine; toe-nailsCases: EORTC quality-of -life questionnaires
Carers: Caregiver Reaction Scale questionnaire
Sample size (eventually) 500 cases; 500 controls; 250 carers
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PanCAM: Clinical Collaborators
Currently, include• Adelaide & Meath Hospital, Tallaght• Cork University Teaching Hospitals
• Bon Secours• St James’ Hospital
• St Vincents’ Healthcare Group
Additional centres
• HSE South-east Hospitals (ethical approval obtained)
• Beaumont (ethical application under review)
• Mater (ethical application being prepared)
• In 2008 - if additional funding secured -• Limerick
• Galway Hospitals
• Royal Victoria Hospital, Belfast• Belfast City Hospital
• Mater Hospital, Belfast
C l i d i i id i l
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Conclusions: descriptive epidemiology
• increase in numbers of cases (population changes); nochange in incidence rates
• projected doubling of numbers of cases by 2020
• long-term fall in mortality rates
• survival improving – mainly surgically-treated patients
• surgical resection rate stable; chemotherapy increasing
C l i i k f
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Conclusions: risk factorsProbably increase risk
• family history
• smoking
• higher BMI
• chronic pancreatitis
• diabetes
Possibly increase risk
• central adiposity
• tooth loss/peridontal
disease
• higher red meat intake
Possibly decrease risk
• higher folate intake
• higher fruit intake
• more physical activity
PanCAM f rther information
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Please contact:
RoI
• Linda Sharp, Epidemiologist and PI: [email protected]; 0214318014• Damian O’Driscoll, Study Co-ordinator (Cork):
[email protected]; 021 4318014
• Mairead Fitzgerald; Study Interviewer (Dublin):[email protected]; 01 4143362
NI
• Liam Murray, Epidemiologist and PI; [email protected] ; 0044 289 063 27602• Karen Galway, Study Co-ordinator; [email protected] ;
00 44 289 063 27602
PanCAM: further information
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