Artikel 4 - Cohort
Artikel 4 - Cohort
Artikel 4 - Cohort
https://doi.org/10.1007/s10552-017-0984-x
BRIEF REPORT
Received: 12 July 2017 / Accepted: 17 November 2017 / Published online: 28 November 2017
© Springer International Publishing AG, part of Springer Nature 2017
Abstract
Purpose Prospective cohort studies suggest that red and processed meat consumption is associated with increased risk of
pancreatic cancer among men, but not women. However, evidence is limited, and less evidence exists for other types of meat.
Methods Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for the asso-
ciation of meat consumption, by type, with pancreatic cancer risk among 138,266 men and women in the Cancer Prevention
Study-II Nutrition Cohort. Diet was assessed at baseline in 1992, and 10 years earlier, at enrollment into the parent CPS-II
mortality cohort. 1,156 pancreatic cancers were verified through 2013.
Results Red meat, processed meat, and fish intake at baseline were not associated with pancreatic cancer risk. However,
for long-term red and processed meat consumption (highest quartiles in 1982 and 1992, vs. lowest quartiles), risk appeared
different in men [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.90, 1.95] and women (HR 0.72, 95% CI 0.47, 1.10,
p heterogeneity by sex = 0.05). Poultry consumption in 1992 was associated with increased pancreatic cancer risk (HR 1.27,
95% CI 1.04, 1.55, p trend = 0.01, top vs. bottom quintile).
Conclusions The associations of meat consumption with pancreatic cancer risk remain unclear and further research, par-
ticularly of long-term intake, is warranted.
Keywords Diet · Meat · Red meat · Processed meat · Pancreatic cancer · Prospective cohort study
13
Vol.:(0123456789)
126 Cancer Causes & Control (2018) 29:125–133
positive associations among men (RR 1.21, 95% CI 1.07, analysis to minimize reverse causation. After these exclu-
1.37 for red and RR 1.18, 95% CI 1.06, 1.31 for processed sions, a total of 138,266 participants comprised the analytic
meat), but not among women. The relationship of other cohort.
types of meat with pancreatic cancer risk is inconsistent, but Of the 1,156 participants with incident pancreatic cancer
positive associations with poultry intake have been observed [International Classification of Disease for Oncology, Third
[6–13]. Edition (Code C250–C259)] in this analysis, 205 (17.7%)
Using data from the Cancer Prevention Study (CPS)-II cases were initially identified by self-report and subse-
Nutrition Cohort, a large U.S. prospective cohort study of quently verified by obtaining medical records (115, 56.1%),
cancer incidence and mortality, we examined associations or by linkage with state cancer registries (90, 43.9%) [14].
of baseline and long-term red and processed meat, poultry, We additionally obtained medical records on three partici-
and fish intake with incident pancreatic cancer, and potential pants (0.3% total) via proxy report and consent. An addi-
differences in associations by sex. tional 941 (81.4%) cases had pancreatic cancer listed as a
primary or contributory cause of death on their death certifi-
cate and were identified through computerized linkage with
Materials and methods the National Death Index [10]; additional information on
524 (55.7%) of these cases was obtained through subsequent
Study participants linkage with state cancer registries. The remaining cases (7,
0.6% total) were identified as a pancreatic cancer case during
The CPS-II Nutrition Cohort is a subset of the parent CPS- verification of another reported cancer. Mean (SD) follow-up
II mortality cohort, a study of cancer mortality including was 15.7 (4.5) years.
1.2 million men and women who completed a brief question-
naire at the time of enrollment in 1982 [14]. In 1992, CPS-II Dietary assessment
mortality cohort participants from 21 states were invited
to enroll in the CPS-II Nutrition Cohort [14]. At baseline Diet was assessed at baseline (i.e., 1992) using a validated,
in 1992, CPS-II Nutrition Cohort participants completed a modified brief Block FFQ [15]. Participants were asked to
mailed self-administered questionnaire providing informa- report average frequency of consumption over the previous
tion on demographic, medical, dietary, and lifestyle factors. year, ranging from never to two or more times per day, and
Follow-up questionnaires to ascertain newly diagnosed can- whether their typical portion was small, medium or large
cers and to update exposure information were sent biennially compared to the medium portion size listed. Meat types
starting in 1997; the response rate to follow-up surveys is included fresh red meat (i.e., hamburgers/ground beef, steak/
consistently 80% or greater. The Emory University Insti- roast, beef stew or pot pie, liver, and pork), processed meat
tutional Review Board approves all aspects of the CPS-II (i.e., hot dogs, lunch meats, sausage, and bacon), poultry
Cohorts. (i.e., chicken or turkey, fried chicken), and fish (i.e., tuna
Of the 184,185 men and women who returned the 1992 and other fish). In 1982, participants reported dietary intake
baseline survey, we excluded those who were lost to fol- on a brief questionnaire as part of the parent CPS-II mortal-
low-up (n = 6,206), reported a history of pancreatic cancer ity cohort. The survey asked “how many days per week do
(n = 42) or cancer other than non-melanoma skin cancer you eat the following foods?” including the following meat
(n = 22,826) at baseline, or whose pancreatic cancer was items: hamburgers, beef, pork, ham, liver; smoked meats,
unverifiable (n = 4), or whose diagnosis date was > 6 months sausage, fried bacon; chicken, and fish. Individuals whose
after self-report (n = 1). We also excluded participants diet questionnaire was considered incomplete (missing the
diagnosed with pancreatic endocrine tumors, sarcomas, entire right or left column of the survey or ≥ 24 of the 28
and lymphomas (histology types 8150–8155, 8240–8246) total line items) were excluded from the analyses using 1982
(n = 23), as the causes of these uncommon pancreatic dietary data (n = 63 cases, n = 7,483 total).
tumors may differ from causes of exocrine tumors. Addi-
tionally, we excluded those who reported total daily energy Statistical analyses
intake < 650 kcal or > 4,000 kcal (men) or < 500 kcal or
> 3,500 kcal (women) (n = 14,749) or who were missing Follow-up time began 2 years following completion of the
answers to ≥ 8 of the 14 meat questions at baseline (n = 213). baseline survey and continued until the date of pancreatic
We also excluded participants who could not contribute cancer diagnosis or pancreatic cancer death if verified only
follow-up time to the analysis (n = 1,855) because they through linkage with NDI, the date of censoring due to loss
died or were diagnosed with pancreatic cancer during the to follow-up, other cause of death, or June 30, 2013, which-
first 2 years of follow-up, which were not included in this ever came first. Individuals who self-reported pancreatic
13
Cancer Causes & Control (2018) 29:125–133 127
cancer that could not be verified were censored at the last consumption had lower educational attainment, higher BMI,
cancer-free survey. and prevalence of diabetes, were more likely to be current
Meat exposures were categorized using sex-specific smokers, and were less physically active than participants
quintiles in 1992, and quartiles in long-term analyses due who ate less red and processed meat. On average, partici-
to smaller numbers. Cox proportional hazards models pants with high consumption of red and processed meat were
were used to evaluate multivariable-adjusted associations more likely to be heavy alcohol drinkers, to consume more
of each exposure with pancreatic cancer risk. All models calories, and to consume a higher proportion of calories
adjusted for age at baseline using the stratified Cox pro- from saturated fat. Poultry and fish intake were only slightly
cedure with 1-year age strata, and models including men lower across higher quintiles of red and processed meat con-
and women controlled for sex. We included the following sumption. Consumption of fruits and vegetables, and the
established risk factors, assessed from the baseline survey, average dietary glycemic index were not markedly different
in all models: smoking status [never, former (≤ 5, > 5–10, across quintiles. However, glycemic load was considerably
> 10–15, and > 15 years since quit), current (< 20 or ≥ 20 lower with a higher meat intake.
cigarettes/day, missing); body mass index (BMI) in kg/m2 Baseline red and processed meat consumption was not
(< 18.5, 18.5–<25, 25–<30, 30+, missing/unknown); his- associated with pancreatic cancer incidence among men
tory of diabetes (no, yes); and ethanol in g per day (0/miss- and women examined separately, or combined (Table 2).
ing, > 0–10, > 10–15, > 15); saturated fat (% kilocalories In analyses of men and women combined, baseline poultry
per day, in quintiles); and total energy (kilocalories per day, consumption was associated with higher pancreatic cancer
in quintiles) were also included]. We examined associations risk (highest vs. the lowest quintile of consumption HR 1.27,
including other types of meat in the models. We also con- 95% CI 1.04–1.55, p trend = 0.01); however, in sex-specific
ducted substitution analyses by including total meat in the analyses, this association was statistically significant only
model, where the beta reflected substitution of the exposure among women (HR 1.45, 95% CI 1.07, 1.95, p trend = 0.03,
of interest for other types of meat in the diet; however, none p heterogeneity by sex = 0.51). There was no consistent pat-
of these additional models changed the results. Education, tern of association between fish intake and pancreatic cancer
race, recreational physical activity, fruits, vegetables, total risk overall or when stratified by sex. Including other types
sugar, and whole grains were considered as covariates but of meat, or total meat, in the models did not change the risk
adjustment for these factors did not change the risk estimates estimates (not shown).
and were therefore not included. When meat intake consistently in the top quartile 10 years
P for trend was calculated using a continuous variable before baseline and at study baseline (relative to intake con-
created from medians within quantile categories. We exam- sistently in the bottom quartile) was considered, no meat
ined heterogeneity in associations by several factors, includ- types were statistically significantly related to risk of devel-
ing sex, smoking status (never, ever), hormone replacement oping pancreatic cancer (Fig. 1). For red meat, processed
therapy (never/ever, women only), </≥ median age at base- meat or both combined, associations among men and women
line, median BMI (sex-specific, kg/m2), and median etha- were qualitatively different, with point estimates were above
nol intake (sex-specific, g per day), using continuous meat 1.0 for men and below 1.0 for women (p heterogeneity by
intake variables (servings per week). sex for red and processed meat combined = 0.05). These
Likelihood ratio tests [16] were used to test violations results were similar when we controlled for BMI in 1982
of the Cox proportional hazards assumption and heteroge- and change in BMI from 1982 to 1992. A positive associa-
neity of associations by modeling multiplicative interac- tion with poultry intake in women only was not statistically
tions between meat and age, sex, smoking history, hormone significant.
replacement therapy use, BMI, and alcohol. All analyses None of the associations with meat intake violated the
were conducted using SAS version 9.2 (SAS Institute, Cary, Cox Proportional Hazards assumption, and no significant
NC). p values were two-sided and considered statistically heterogeneity of associations was observed by age, smok-
significant if < 0.05. ing history, hormone replacement therapy use, alcohol con-
sumption, or BMI.
Results
Discussion
At baseline, women consumed red and processed meat less
often, and poultry slightly more often, than men (Table 1). In this prospective cohort study of 138,266 U.S. adults, we
The difference in meat servings per week between the found no evidence of an association between baseline con-
highest and lowest quintiles varied 10- and 14-fold in men sumption of unprocessed red meat or processed meat and
and women, respectively. Men and women with higher pancreatic cancer risk in both sexes. When we considered
13
128 Cancer Causes & Control (2018) 29:125–133
Table 1 Baseline characteristics by red and processed meat intake among 138,266 men and women in the Cancer Prevention Study II Nutrition
Cohort, 1992–2013
Red/processed meat intake quintile (servings/week)
Men Women
Q1: ≤2.4 Q3: >4.2–6.2 Q5: >9.1 Q1: ≤1.3 Q3: >2.6–3.9 Q5: >5.9
Sociodemographic characteristic
N per category 13,060 12,905 12,965 14,767 14,641 14,681
Mean (SD) age (years) 64.1 (6.2) 63.8 (6.0) 63.0 (5.8) 62.3 (6.6) 61.8 (6.5) 61.4 (6.5)
Race
White, white-Hispanic 96.9 97.7 97.7 96.9 97.7 97.6
Black, black-Hispanic 1.0 1.1 1.2 1.4 1.2 1.5
Unknown, other or not reported 2.0 1.2 1.0 1.7 1.1 0.9
Education
Less than high school 4.4 7.0 11.4 3.1 4.5 6.2
High school graduate 12.9 18.1 26.0 24.8 31.7 37.2
Some college, trade school 23.2 25.8 28.4 33.4 31.4 31.5
College graduate 59.5 49.1 34.2 38.7 32.4 25.1
Body mass index (kg/m2)
<18.5 0.5 0.4 0.4 2.8 1.4 1.1
18.5–<25 47.6 34.4 25.6 61.6 50.9 37.4
25–<30 43.2 50.9 50.9 24.9 31.9 35.5
≥30 7.5 13.1 21.5 9.1 14.2 24.3
Missing 1.3 1.3 1.6 1.5 1.5 1.6
History of diabetes (% yes) 7.2 8.9 12.0 5.2 5.7 8.7
Smoking status
Never 37.6 33.3 27.5 52.9 55.0 56.0
Current, < 20 cigarettes/day 2.3 3.9 5.5 3.4 4.6 5.8
Current, ≥ 20 cigarettes/day 1.5 4.2 9.1 1.8 3.5 5.9
Former, ≤ 5 years since quit 4.2 6.1 7.8 4.3 5.1 5.3
Former, > 5–10 years since quit 5.1 6.2 6.9 4.6 4.6 4.1
Former, > 10–15 years since quit 6.2 6.5 6.9 4.9 4.3 3.5
Former, > 15 years since quit 40.7 37.7 34.1 25.7 20.7 17.5
Missing 2.3 2.1 2.3 2.4 2.3 1.9
Physical activity (MET-h/week) a
0 7.0 11.2 17.9 6.3 8.5 12.7
>0–<17.5 56.4 58.7 54.3 60.7 66.4 64.7
≥17.5 35.9 29.1 26.6 32.0 24.2 21.6
Missing 0.7 1.0 1.2 1.0 0.9 1.0
Dietary characteristic
Ethanol intake (g/day)
0 37.0 33.1 34.8 50.0 45.8 49.3
>0–10 35.3 33.6 31.6 36.7 37.7 34.4
>10–15 9.4 9.2 8.8 6.8 7.5 6.7
>15 18.3 24.1 24.8 6.6 9.0 9.6
Mean (SD)
Energy intake (kcal/day) 1,403.9 (458.4) 1,730.4 (490.6) 2,377.5 (608.9) 1,115.3 (382.3) 1,305.9 (398.9) 1,752.2 (497.8)
Red and processed meat intake 1.2 (0.8) 5.2 (0.6) 12.9 (3.9) 0.6 (0.4) 3.2 (0.4) 8.7 (2.9)
(servings/week)
Red meat (servings/week) 0.9 (0.6) 3.1 (1.1) 6.6 (3.1) 0.5 (0.4) 2.2 (0.7) 5.1 (2.4)
Processed meat (servings/week) 0.3 (0.4) 2.0 (1.1) 6.3 (3.6) 0.1 (0.2) 1.0 (0.7) 3.5 (2.4)
Poultry intake (servings/week) 2.4 (2.2) 2.0 (1.6) 2.2 (1.8) 2.3 (2.0) 2.0 (1.6) 2.2 (1.7)
13
Cancer Causes & Control (2018) 29:125–133 129
Table 1 (continued)
Mean (SD)
Fish intake (servings/week) 2.0 (2.0) 1.6 (1.4) 1.5 (1.4) 1.7 (1.8) 1.4 (1.4) 1.5 (1.4)
Saturated fat (as % of energy) 8.6 (3.0) 11.8 (2.7) 14.1 (2.7) 8.0 (3.0) 10.7 (3.0) 13.2 (2.9)
Fruit intake (servings/day) 1.5 (1.2) 1.2 (1.0) 1.2 (1.0) 1.5 (1.1) 1.3 (1.0) 1.2 (0.9)
Vegetable intake (servings/day) 2.1 (1.4) 1.9 (1.1) 2.1 (1.2) 2.3 (1.5) 2.0 (1.2) 2.2 (1.2)
Energy-adjusted glycemic index 76.3 (9.3) 75.2 (8.3) 76.0 (8.3) 74.2 (8.7) 74.2 (7.4) 74.9 (7.1)
Energy-adjusted glycemic load 164.1 (34.9) 142.0 (28.9) 131.8 (27.4) 127.6 (24.3) 112.9 (20.9) 102.2 (18.9)
All values are percentages unless otherwise indicated; some percentages do not add up to 100% due to missing data or rounding
MET metabolic equivalent, SD standard deviation
a
Metabolic equivalents (METS) are defined for each type of exercise-related physical activity as a multiple of metabolic equivalent of sitting
quietly for 1 h
red and processed meat intake at baseline and 10 years ear- A potential role of red and processed meat consumption
lier, qualitative differences in risk estimates by sex were in pancreatic cancer etiology is plausible because 95% of
observed, but associations did not reach statistical signifi- pancreatic cancers arise in exocrine cells, which produce
cance. For poultry intake, men and women in the highest enzymes for digestion [1]. Fat and protein in the diet stimu-
vs. lowest quintile at baseline had a statistically significant late the release of cholecystokinin in the duodenum, which
27% higher risk of pancreatic cancer; this association was in turn stimulates the release of pancreatic enzymes [20]. In
stronger in women than men. Neither baseline nor long-term animal experiments, a high-fat diet causes overproduction of
fish consumption was associated with pancreatic cancer risk. pancreatic juices, leading to pancreatitis [20], an established
Red and processed meats are considered probable and cause of pancreatic adenocarcinoma [21]. Other potential
definite carcinogens, respectively, by IARC based on a mechanisms for meat intake may involve DNA-damaging
review of mechanistic and human evidence for colorectal heterocyclic amines and polycyclic aromatic hydrocarbons
cancer [4]. However, the evidence for a positive associa- in cooked meat, heme iron, and exogenously or endog-
tion of red and processed meat with pancreatic cancer risk enously formed nitrosamines [19, 22].
was considered inconclusive [4]. Similarly, the WCRF/ The reasons for qualitatively different associations by sex
AICR concluded that the evidence was “limited/suggestive” for long-term red and processed meat intake with pancre-
[3]. Our overall findings do not support an association of atic cancer risk observed in this and other studies [5, 17]
red and processed meat consumption and pancreatic can- are unclear. In CPS-II, men reported consuming more red
cer risk. The direction of associations in men and women and processed meat compared to women, but it is unknown
observed for long-term red and processed meat consumption whether relevant thresholds of exposure exist. Differential
(p heterogeneity by sex = 0.05) was in directions consistent lifetime iron stores in men and women, which influences free
with prior literature, although numbers were limited in this serum iron levels and percent transferrin saturation, were
analysis and results were not statistically significant. Two previously suggested as a potential explanation for increased
previous meta-analyses reported significant heterogeneity risk in men but not women in the NIH-AARP cohort [10].
by sex in the association of red or processed meat and pan- Higher serum iron and iron saturation were associated
creatic cancer risk [5, 17]. A 2016 meta-analysis [5] of 16 with subsequent pancreatic cancer risk in an exploratory
prospective cohort studies reported statistically significant case–control study of San Francisco Bay area residents who
increased pancreatic cancer risk for “high” versus “low” received health check-ups [23]; additional research is needed
red meat consumption among men (RR 1.21, 95% CI 1.07, to confirm, or refute, a sex difference in this association,
1.37) but not women (RR 1.06, 95% CI 0.85,1.31); similar and to identify potential underlying mechanisms if it exists.
findings were reported for processed meat among men and In the current study, high poultry intake (i.e., a median
women from 20 cohorts (RR 1.18, 95% CI 1.06, 1.31 and of 5.3 servings/week) was associated with a 27% increased
RR 0.99, 95% CI 0.84, 1.16, respectively). Although four risk of pancreatic cancer as compared to low intake (i.e.,
of the studies included in these meta-analyses were of dif- a median of 0.6 servings/week), which appeared to be
ferent meat exposures from the NIH-AARP cohort [10, 13, driven mainly by a 45% increased risk of pancreatic cancer
18, 19], with different periods of follow-up, an earlier meta- among women (p heterogeneity by sex = 0.51). While this
analysis including only one publication from NIH-AARP finding was unexpected, it is consistent with the published
also observed a statistically significant positive association literature. Of eight prospective studies that examined the
in men, but not women [17]. associations of poultry, chicken and/or “white meat” with
13
Table 2 Multivariable-adjusted hazard ratios and 95% confidence intervals for incident pancreatic cancer by 1992 meat intake among men and women in the Cancer Prevention Study II Nutri-
130
13
(servings/week) a a
Cases Person-years HR (95% CI) Median (serv- Cases Person-years HR (95% CI) Median (serv- Cases Person-years HR (95% CI)a
ings/week) ings/week)
Multivariable model adjusted for age in 1992, gender (combined models only), 1992 body mass index, 1992 history of diabetes, 1992 smoking status, 1992 ethanol intake, 1992 energy intake
0.94 (0.70, 1.26)
were positive [6–13], and two of these were statistically sig-
HR (95% CI)a nificant [11, 13]. Among men and women in the European
Prospective Investigation of Cancer, Rorhmann et al. [11]
0.60
reported a statistically significant 24% higher risk of pan-
creatic cancer per 50 g per day increase in poultry intake
Person-years
Meat intake quintiles in all models use gender-specific cut-points (men/women); p value for heterogeneity by gender > 0.05 for all meat types
of pancreatic cancer.
Combined
13
132 Cancer Causes & Control (2018) 29:125–133
0.1 1 10
HR (95% CI) Men Women
Fig. 1 Multivariable-adjusted hazard ratios (HR) and 95% Confi- ing status in 1992, ethanol intake in 1992, energy intake and % satu-
dence Intervals (CI) for incident pancreatic cancer among men (filled rated fat intake in 1992, and BMI in 1992. Numbers of cases provided
diamond) and women (filled circle) with consistently high versus low are those with consistently high meat intake. For the reference group
long-term (1982 and 1992) Meat Intake, Cancer Prevention Study (quartile 1 at both time points), case numbers were as follows: red/
II Nutrition Cohort, 1992–2013. Results presented are for highest processed meat (n = 75 men, n = 81 women); red meat (n = 69 men,
sex-specific quartile in both 1982 and 1992 compared to the refer- n = 84 women); processed meat (n = 75 men, n = 84 women); poultry
ence category of lowest quartile in both time periods. Multivariable (n = 50 men, n = 34 women); fish (n = 42 men, n = 48 women). *p het-
models adjusted for age in 1992, history of diabetes in 1992, smok- erogeneity by sex = 0.05
In conclusion, these findings do not support a delete- Disclaimer The views expressed here are those of the authors and do
rious effect of red and processed meat consumption on not necessarily represent the American Cancer Society or the American
Cancer Society—Cancer Action Network.
pancreatic cancer risk; however, we cannot rule out an
association in men as suggested by previous studies. The
positive association observed with higher poultry con-
sumption deserves further study.
References
Acknowledgments The authors express sincere appreciation to all
Cancer Prevention Study-II participants, and to each member of the 1. American Cancer Society (2017) Cancer facts & figures, 2017.
study and biospecimen management group. The authors would like to American Cancer Society, Atlanta
acknowledge the contribution to this study from central cancer regis- 2. Yachida S, Jones S, Bozic I et al (2010) Distant metastasis occurs
tries supported through the Centers for Disease Control and Preven- late during the genetic evolution of pancreatic cancer. Nature
tion’s National Program of Cancer Registries and cancer registries 467:1114–1117
supported by the National Cancer Institute’s Surveillance Epidemiol- 3. WCRF/AICR (2012) Continuous update project report: diet, nutri-
ogy and End Results Program. The American Cancer Society supports tion, physical activity, and pancreatic cancer 2012. WCRF/AICR,
the maintenance and follow-up of the Cancer Prevention Studies. The Washington DC
American Cancer Society also supported all investigators during the 4. Bouvard V, Loomis D, Guyton KZ et al (2015) Carcinogenicity of
conduct of this analysis. consumption of red and processed meat. Lancet 16(16):1599–1600
5. Zhao Z, Yin Z, Pu Z, Zhao Q (2016) Association between con-
sumption of red and processed meat and pancreatic cancer risk-a
Compliance with ethical standards systematic review and meta-analysis. Clin Gastroenterol Hepatol
15(4):486–493
Conflict of interest The authors declare that they have no conflict of 6. Zheng W, McLaughlin JK, Gridley G et al (1993) A cohort
interest. study of smoking, alcohol consumption, and dietary factors
13
Cancer Causes & Control (2018) 29:125–133 133
for pancreatic cancer (United States). Cancer Causes Control 18. Jiao L, Stolzenberg-Solomon R, Zimmerman TP et al (2015)
4:477–482 Dietary consumption of advanced glycation end products and
7. Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, pancreatic cancer in the prospective NIH-AARP Diet and Health
Albanes D (2002) Prospective study of diet and pancreatic cancer Study. Am J Clin Nutr 101:126–134
in male smokers. Am J Epidemiol 155:783–792 19. Aschebrook-Kilfoy B, Cross AJ, Stolzenberg-Solomon RZ et al
8. Larsson SC, Hakanson N, Permert J, Wolk A (2006) Meat, fish, (2011) Pancreatic cancer and exposure to dietary nitrate and
poultry and egg consumption in relation to risk of pancreatic can- nitrite in the NIH-AARP Diet and Health Study. Am J Epidemiol
cer: a prospective study. Int J Cancer 118:2866–2870 174:305–315
9. Lin Y, Kikuchi S, Tamakoshi A et al (2006) Dietary habits and 20. Matters GL, Cooper TK, McGovern CO et al (2014) Cholecys-
pancreatic cancer risk in a cohort of middle-aged and elderly Japa- tokinin mediates progression and metastasis of pancreatic cancer
nese. Nutr Cancer 56:40–49 associated with dietary fat. Dig Dis Sci 59:1180–1191
10. Stolzenberg-Solomon RZ, Cross AJ, Silverman DT et al (2007) 21. Ryan DP, Hong TS, Bardeesy N (2014) Pancreatic adenocarci-
Meat and meat-mutagen intake and pancreatic cancer risk noma. New Engl J Med 371:2140–2141
in the NIH-AARP cohort. Cancer Epidemiol Biomark Prev 22. Anderson KE, Mongin SJ, Sinha R et al (2012) Pancreatic can-
16:2664–2675 cer risk: associations with meat-derived carcinogen intake in the
11. Rohrmann S, Linseisen J, Nothlings U et al (2013) Meat and fish Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
consumption and risk of pancreatic cancer: results from the Euro- (PLCO) cohort. Mol Carcinog 51: 128–137
pean Prospective Investigation into Cancer and Nutrition. Int J 23. Friedman GD, van den Eeden SK (1993) Risk factors for pancre-
Cancer 132:617–624 atic cancer: an exploratory study. Int J Epidemiol 22:30–37
12. Ghorbani Z, Pourshams A, Fazeltabar Malekshah A, Sharafkhah 24. Nothlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson
M, Poustchi H, Hekmatdoost A (2016) Major dietary protein BE, Kolonel LN (2005) Meat and fat intake as risk factors for
sources in relation to pancreatic cancer: a large prospective study. pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst
Arch Iran Med 19:248–256 97:1458–1465
13. Taunk P, Hecht E, Stolzenberg-Solomon R (2016) Are meat and 25. Food US and Drug Administration (2015) Arsenic-based animal
heme iron intake associated with pancreatic cancer? Results drugs and poultry. U.S. Department of Health and Human Ser-
from the NIH-AARP diet and health cohort. Int J Cancer vices, New York
138:2172–2189 26. Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien
14. Calle EE, Rodriguez C, Jacobs EJ et al (2002) The American A (2017) Poultry consumption and arsenic exposure in the U.S.
Cancer Society Cancer Prevention Study II Nutrition Cohort— Population. Environ Health Perspect 125:370–377
rationale, study design, and baseline characteristics. Cancer 27. Liu-Mares W, Mackinnon JA, Sherman R et al (2013) Pancreatic
94:2490–2501 cancer clusters and arsenic-contaminated drinking water wells in
15. Flagg EW, Coates RJ, Calle EE, Potischman N, Thun MJ (2000) Florida. BMC Cancer 13:111
Validation of the American Cancer Society Cancer Prevention 28. Nachman KE, Ginsberg GL, Miller MD, Murray CJ, Nigra AE,
Study II Nutrition Survey Cohort Food Frequency Questionnaire. Pendergrast CB. (2017) Mitigating dietary arsenic exposure:
Epidemiology 11:462–468 Current status in the United States and recommendations for an
16. Kleinbaum DG, Kupper LL, Muller KE (1988) Applied regres- improved path forward. Sci Total Environ 581–582:221–236
sion analysis and other multivariable methods. Duxbury Press, 29. IARC (2012) Arsenic, metals, fibres, and dusts. IARC, Lyon
Belmont 30. Ojajarvi IA, Partanen TJ, Ahlbom A et al (2000) Occupational
17. Larsson SC, Wolk A (2012) Red and processed meat consump- exposures and pancreatic cancer: a meta-analysis. Occup Environ
tion and risk of pancreatic cancer: meta-analysis of prospective Med 57:316–324
studies. Br J Cancer 106:603–607
13