Incident Pancreatic Cancer Cases Research Articles

Prospective analysis of association between statins and pancreatic cancer risk in the Women's Health Initiative.

To determine whether HMG-CoA reductase inhibitors (statins) are associated with a lower risk of pancreatic cancer. The population included 160,578 postmenopausal women enrolled in the Women's Health Initiative (WHI) in which 385 incident cases of pancreatic cancer were identified over an average of 8.69 (SD ±4.59) years. All diagnoses were confirmed by medical record and pathology review. Information on statin use and other risk factors was collected at baseline and during follow-up. Multivariable-adjusted hazards ratios (HRs) and 95 % confidence intervals (CIs) evaluating the relationship between prior statin use (at baseline only as well as in a time-dependent manner) and risk of pancreatic cancer were computed from Cox proportional hazards regression analyses after adjusting for appropriate confounders. We also evaluated the effect of statin type, potency, lipophilic status, and duration of use. All statistical tests were two-sided. Statins were used at baseline by 12,243 (7.5 %) women. The annualized rate of pancreatic cancer in statin users and nonusers, respectively, was 0.0298 versus 0.0271 %. The multivariable-adjusted HR for statin users versus nonusers at baseline was 0.92 and 95 % CI 0.57-1.48. In a time-dependent model, the HR for low-potency statins was 0.46, 95 % CI 0.20-1.04. There was no significant effect seen by statin lipophilicity or duration of use. There was no significant relationship between statins and pancreatic cancer risk in the WHI; however, there was a marginal inverse association noted for low-potency statins. Analyses of larger numbers of cases are needed to further explore this relationship.

Dietary Intake of One-Carbon Metabolism-Related Nutrients and Pancreatic Cancer Risk: The Singapore Chinese Health Study.

Nutrients involved in one-carbon metabolism are hypothesized to protect against pancreatic cancer development. The Singapore Chinese Health Study database was used to prospectively examine the association between intake of one-carbon metabolism-related nutrients and pancreatic cancer risk. Between 1993 and 1998, 63,257 men and women ages 45 to 74 years were enrolled into the cohort. The daily intakes of the following one-carbon metabolism-related nutrients were assessed at enrollment using a 165-item food frequency questionnaire: betaine, choline, folate, and vitamins B2, B6, and B12. Multivariable HRs and 95% confidence intervals (CI) for pancreatic cancer risk associated with dietary intakes of one-carbon metabolism-related nutrients were calculated. As of December 2013, 271 incident pancreatic cancer cases were identified during an average of 16.3 years of follow-up. Higher intakes of vitamin B6 and choline were associated with statistically significant decreases in the risk of developing pancreatic cancer. Compared with the lowest quartile, HRs (95% CIs) for the highest quartiles of vitamin B6 and choline were 0.52 (0.36-0.74; P trend = 0.001) and 0.67 (0.48-0.93; P trend = 0.04), respectively. There were no clear associations between the other one-carbon metabolism-related nutrients and pancreatic cancer risk. Our study suggests that higher intake of vitamin B6 and choline may lower the risk of pancreatic cancer. Our prospective findings are consistent with the in vivo evidence for protective roles of vitamin B6 and choline on pancreatic cancer development.

Abstract 1882: Dietary intake of vitamin B6 and choline are inversely associated with pancreatic cancer risk: The Singapore Chinese Health Study

Abstract Background. Dietary nutrients involved in one-carbon metabolism, either as methyl donors or as enzyme co-factors are hypothesized to protect against pancreatic cancer development. Animal studies showed that diets deficient in one carbon metabolism-related nutrients, such as vitamin B6 and choline, were able to induce DNA damage in the pancreas and enhance the development of carcinogen-initiated pancreatic cancers in rodents. Although there is a strong rationale that one carbon metabolism-related nutrients may alter pancreatic cancer risk in human, prospective studies with well-characterized dietary intake that test the hypothesis are lacking. Methods. Between 1993 and 1998, 63,257 men and women aged 45-74 years were recruited into the Singapore Chinese Health Study. By the end of 2013, 271 incident pancreatic cancer cases were identified during up to 20 years of follow-up, after excluding individuals with extreme calorie intake or a history of cancer at enrollment (N = 2,959). The daily intakes of betaine, choline, folate, methionine, and vitamins B2, B6 & B12 were assessed at baseline by a 165-item semi-quantitative food frequency questionnaire that was developed for, and validated in the study population. Hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with total calorie-adjusted intake levels of one carbon nutrients were calculated using the Cox-proportional hazard regression method with the adjustment for established risk factors for pancreatic cancer including age, sex, body mass index (BMI), smoking, alcohol drinking, and diabetes. Results. Higher intake of vitamin B6 and choline were associated with a statistically significant decrease in the risk of developing pancreatic cancer. Compared with the lowest quartile, HRs (95% CIs) for the 2nd, 3rd, and 4th quartiles of vitamin B6 were 0.71 (0.51-0.98), 0.80 (0.58-1.11), and 0.52 (0.36-0.74), respectively (P trend = 0.001). Similarly, the corresponding HRs (95% CIs) for choline were 0.57 (0.40-0.80), 0.72 (0.52-1.00), and 0.67 (0.48-0.93), respectively (P trend = 0.04). There was no overall statistically significant relationship between dietary intake of betaine, folate, methionine, vitamins B2 or B12 and pancreatic cancer risk. In stratified analyses by sex, the statistically significant, inverse associations between dietary choline and vitamin B6 and pancreatic cancer risk were present among men only (both P trend ≤0.02). Among men, these inverse associations were more apparent in smokers and nondrinkers of alcoholic beverages. Conclusion. Our prospective findings are consistent with in vivo evidence for protective roles of vitamin B6 and choline on pancreatic cancer development. These dietary compounds may be developed as potential chemopreventive agents against pancreatic cancer development in humans. Citation Format: Joyce Y. Huang, Lesley M. Butler, Renwei Wang, Ai Zhen Jin, Woon-Puay Koh, Jian-Min Yuan. Dietary intake of vitamin B6 and choline are inversely associated with pancreatic cancer risk: The Singapore Chinese Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1882. doi:10.1158/1538-7445.AM2015-1882

PWE-205 Meat and the risk of pancreatic cancer: a prospective cohort study (EPIC-NORFOLK) using data from food diaries

<h3>Introduction</h3> Processed, red and white meat intake may be involved in the aetiology of pancreatic cancer as they can contain carcinogens including nitrosamines, which may influence the natural history of the cancer at different ages. The data from epidemiological studies are conflicting, possibly due to lack of generalisability and inaccurate measures of diet. We investigated associations between processed, red and white meat intake and pancreatic cancer, for the first time using data from 7-day food diaries (7-DFDs), the most accurate questionnaire-based nutritional assessment. <h3>Method</h3> 23,658 participants recruited into the EPIC-Norfolk Study completed 7-DFDs and were followed up over 17 years to identify incident cases of pancreatic cancer. Meat intakes were divided into quintiles and compared with a sample of 3970 controls. Hazard ratios (HR) were calculated for developing pancreatic cancer for each quintile and for trends across quintiles, adjusted for age, sex, smoking, diabetes, and energy intake. A sub-group analysis was performed in participants younger and older than 60 years at recruitment. <h3>Results</h3> During follow-up, 86 participants (0.36%) were diagnosed with pancreatic cancer (56% women). The median age at diagnosis was 73.4 years with a median survival of 4 months (inter-quartile range= 2–7 months). In the whole cohort, there were no associations with any quintiles of processed, red or white meats or for trends across quintiles. However, in participants younger than 60 years at recruitment, all quintiles of processed and red meat intakes were borderline significantly positively associated with risk (Q1 vs Q5, HR=3.73, 95% CI=0.95–14.66, p = 0.06 and Q1 vs Q5, HR=4.62, 95% CI=0.96–22.30, p = 0.06) respectively, with trends across quintiles for both (HR_trend=1.37, 95% CI=1.04–1.82 and HR_trend=1.33, 95% CI=1.00–1.77). For participants older than 60, there were no significant effects for either processed or red meats. For white meat, there was a positive association for all ages in quintiles two (HR=2.44, 95% CI=1.12–4.91) and four (HR=2.47, 95% CI=1.25–4.91), but no trend. There were no associations for white meat intake in those younger than 60 but the effects remained if older than 60. <h3>Conclusion</h3> The findings suggest that processed and red meats may be involved in the aetiology of pancreatic cancer. As the associations are related to consumption before the age of 60 years, these meats may influence the development of precursor lesions for pancreatic cancer, such as pancreatic intraepithelial neoplasia (PanINs). The effects of white meat are uncertain. Processed and red meat intakes should be measured in aetiological studies, and reducing intake could reduce the incidence of pancreatic cancer. <h3>Disclosure of interest</h3> None Declared.

Tu1941 Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study

Background: We examined the association between opium consumption and pancreatic cancer incidence in a large-scale prospective cohort of the general population in northeastern Iran. Methods: A total of 50,045 adults were systematically followed up (median of 7.4 years), and incident cases of pancreatic cancer were identified. Self-reported data on opium consumption was collected at baseline. Cumulative use (-year) was defined as number of nokhods (a local unit, approximately 0.2 g) of opium consumed per day multiplied by number of years consuming. Adjusted HRs and 95 confidence intervals (CIs) for the association between opium consumption and pancreatic cancer were calculated using Cox proportional hazards regression models. Results: Overall, 54 confirmed cases of pancreatic cancer were identified. Opium use of more than 81 nokhod-years (high cumulative use), compared with never use, was strongly associated with pancreatic cancer even after adjustments for multiple potential confounding factors HR = 3.01; 95% CI, 1.25-7.26. High cumulative consumption of opium was significantly associated with risk of pancreatic cancer after adjusting for cumulative dose of cigarette smoking HR = 3.56; 95% CI, 1.49-8.50. In a sensitivity analysis, we excluded participants (including 2 pancreatic cancer cases) who were recruited within the first 5 years of starting opium consumption; high cumulative use of opium was still associated with pancreatic cancer risk HR = 2.75; 95% CI, 1.14-6.64. Conclusions: Our results showed a positive association between opium consumption and pancreatic cancer. Impact: This is the first prospective large-scale study to show the association of opium consumption with pancreatic cancer as a risk factor. © 2017 American Association for Cancer Research.

Interaction of Serum microRNAs and Serum Folate With the Susceptibility to Pancreatic Cancer.

ObjectivesThe aim of this study was to investigate whether 6 candidate serum miRNAs and their interactions with serum folate level were associated with the risk for pancreatic cancer (PC).MethodA hospital-based case-control study including 74 incident PC cases and 74 controls was conducted. Serum folate and miRNAs were determined by radioimmunoassay and real-time quantitative polymerase chain reaction, respectively. Cell lines AsPC-1 and PANC-1 were used for in vitro study.ResultsMiR-16 was elevated (P = 0.030–0.043) and miR-103 was reduced (P = 0.018–0.020) in PC after adjustment for age, sex, and smoking; however, after additional adjustment for folate, only miR-103 was significantly different between cases and controls (P = 0.010). After converting the relative expression of miRNAs into binary variables and adjusting for age, sex, smoking, and folate, the subjects with low miR-103 or low miR-601 were observed to have a higher risk for PC, with odds ratios of 2.33 (95% confidence interval, 1.06–5.10) and 2.37 (95% confidence interval, 1.07–5.26), respectively. Multifactor dimensionality reduction analysis showed a significant interaction for miR-16, folate, and smoking (cross-validation consistency, 10/10; mean testing accuracy, 0.696; P = 0.013). Interaction between miR-16 and folate was also verified in the AsPC-1 cells.ConclusionSerum miR-103; miR-601; and interactions among serum miR-16, folate, and smoking are associated with PC.

Abstract 2916: Childhood BMI is associated with risk of adult pancreatic cancer

Abstract The incidence and death rate for pancreatic cancer, the fourth leading cause of cancer death in the U.S., have been increasing. Excess weight through adulthood is one of the few modifiable risk factors for pancreatic cancer. Childhood obesity rates have increased more rapidly that adulthood obesity in the U.S, but its effects on pancreatic cancer risk are not clear. Hence, the objective of this study is to test the hypothesis that childhood weight is associated with pancreatic cancer risk later in life. We evaluated the association of body mass index (BMI) measured at ages 7-13 with risk of pancreatic cancer later in life in 288,423 children from the Copenhagen School Health Records Register who were born between 1930-1981. These data were linked with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1977-2011. Follow-up ended on the date of pancreatic cancer diagnosis, death, emigration, 70th birthday, or December 31st 2010, whichever came first. Hazard Ratios (HR) and 95% confidence intervals (CI) were calculated for age specific BMI z-scores using Cox proportional hazards stratified on birth cohort and gender. Restricted cubic splines analysis was used to test for linearity. There were 1163 pancreatic cancer cases during the 6,918,420 person-years of follow up. Childhood BMI was associated with pancreatic cancer risk in males and females. At age 10, for example, HR per one unit increase in BMI z-scores was 1.17 (CI: 1.08, 1.26). The observed association did not deviate from linearity. Our results support the hypothesis that higher childhood body weight is associated with increased pancreatic cancer risk later in life. Citation Format: Leticia M. Nogueira, Rachael Stolzenberg-Solomon, Michael Gamborg, Thorkild Sørensen, Jennifer Baker. Childhood BMI is associated with risk of adult pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2916. doi:10.1158/1538-7445.AM2014-2916

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Nut consumption and risk of pancreatic cancer in women

Background:Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer.Methods:We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.Results:We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables.Conclusion:Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.

Duration of diabetes and pancreatic cancer in a case-control study in the Midwest and the Iowa Women's Health Study (IWHS) cohort.

Studies have shown a relationship between history of diabetes and the risk of pancreatic cancer; however, the temporal relation between diabetes and pancreatic cancer is not clearly established. Diabetes and diabetes duration were examined in relation to pancreatic cancer in a population-based case-control study and prospective cohort. Case-control study: pancreatic cancer cases (n=200) from the Midwest were frequency matched by age and sex to population controls (n=673). Logistic regression yielded odds ratios (ORs) and 95% confidence intervals (95% CI). Iowa Women's Health Study (IWHS) cohort: 292 incident pancreatic cancer cases occurred between 1986-2008 among 36,084 post-menopausal, initially cancer-free women. Diabetes status and diagnosis age were ascertained at baseline and follow-ups. Proportional hazards regression yielded hazard ratios (HR, 95% CI) for pancreatic cancer in relation to baseline diabetes. Time-dependent analyses accounted for diabetes diagnosed after baseline. A nested-case control analysis assessed diabetes duration as a risk factor. In the case-control study, compared to participants without diabetes, the multivariate ORs (95% CI) for pancreatic cancer were 2.35 (1.24-4.47) for those with diabetes and 4.00 (0.94-16.9), 2.79 (0.97-8.04), and 2.40 (0.97-5.98) for diabetes durations of 2-5 years, 5.1-10 years, and more than 10 years, respectively. In IWHS, compared to no diabetes, multivariate-adjusted HRs for pancreatic cancer were 1.86 (1.23-2.83) for baseline diabetes and 1.94 (1.40-2.69) adding diabetes during follow-up. In an IWHS nested case-control analysis, ORs were 1.70 (0.78-3.67), 2.62 (1.48-4.65), and 2.10 (1.36-3.24) for diabetes durations of 2-5 years, 5.1-10 years and more than 10 years, respectively, versus no diabetes. Diabetes is associated with pancreatic cancer risk and this is similar across different duration categories.

Abstract 4811: Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition.

Abstract Background: Pancreatic cancer (PC) has an exceptionally high mortality rate due to late discovery and poor prognosis. The etiology of the cancer is largely unknown and primary prevention strategies are limited for this lethal cancer. Over the past years, evidence has been accumulated for folate which may play a role in carcinogenesis. Previous epidemiological studies, however, have shown inconsistent results in relation to PC risk with a weak inverse association with folate intake from foods, but not from supplements. The recent large study from the Pooling Project found no association between folate intake and PC risk. However, in the pooled analysis, folate data may be heterogeneous across studies and countries, thus not readily comparable. In the EPIC study, we obtained dietary folate intake data that was standardized across 10 participating countries using the EPIC Nutrient DataBase. Folic acid fortification or supplementation use was not common in Europe at the baseline data collection. We then set out to evaluate the association between total dietary folate intake and PC risk. Methods: A total of 477,245 participants without any history of cancer and with complete dietary folate information ascertained by food frequency questionnaire were followed up for 11 years, during which 904 first incident primary PC cases were recorded. Folate intake was energy-adjusted by using the residual method. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: In multivariable analyses stratified by age, sex, study center and adjusted for smoking status, energy intake, BMI, educational level, diabetes status, supplement use and dietary fiber intake, we observed non-significantly decreased PC risk with higher folate intake: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest quartile (&amp;lt;240 μg/d) was 0.65 (95% CI: 0.37, 1.13; Ptrend = 0.13). There was a borderline significant and positive trend in PC risk across folate quartiles among current smokers (HR=1.53 (0.59-3.97) for 240-291 μg/d, 3.51 (1.04-11.90) for 291-353 μg/d, and 3.31 (0.71-15.40) for ≥353 μg/d of folate intake, respectively (Ptrend = 0.07)). A similar pattern was shown when a single reference category was chosen and joint effects were determined for tertiles of folate in combination with smoking categories in relation to PC risk. When very low (&amp;lt;150 μg/d) or high intake (≥500 μg/d) were investigated using 200-300 μg/d as a reference, we found a slightly increased, but statistically non-significant risk estimate with a very low intake (HR=1.28, 95% CI: 0.40-4.06). Conclusions: We found non-significant inverse associations between dietary folate intake and PC risk in the large European study. There was some evidence that the findings were heterogeneous by smoking status. Our results warrant further investigation. Citation Format: Jin Young Park, H.B(as) Bueno-de-Mesquita, Pietro Ferrari, Paolo Vineis, Elisabete Weiderpass, Nadia Slimani, for the EPIC Study Group. Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4811. doi:10.1158/1538-7445.AM2013-4811

Abstract 4809: Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Abstract Background: Some published studies on dietary fat and risk of pancreatic cancer suggest that dietary fat and specific fat sources may increase risk of pancreatic cancer. Methods: We examined the association between fat intake (measured by food frequency questionnaire) and pancreatic cancer risk among 111,416 participants in the PLCO Cancer Screening Trial using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: There were 411 incident pancreatic cancer cases over the median 8.9 years of follow up. We observed an inverse association between saturated fat intake and pancreatic cancer risk comparing extreme quintiles (HR=0.64, 95% CI 0.46-0.88), but the association became weaker and non-significant when excluding individuals with &amp;lt;4 years of follow up to assess reverse causation HR=0.88 (95% CI 0.58-1.33). Total fat intake showed a similar pattern of association, while monounsaturated and polyunsaturated fat intakes and analysis by animal or plant source showed no association with risk. Conclusions: Despite more cases and longer follow up than most previous studies, our results do not suggest that higher fat consumption increases risk of pancreatic cancer. Lower fat intake in cases prior to diagnosis may reflect early manifestations of the disease (e.g. dyspepsia), and avoidance of fat which can exacerbate symptoms. Citation Format: Hannah E. Arem, Susan T. Mayne, Joshua Sampson, Harvey Risch, Rachael Z. Stolzenberg-Solomon. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4809. doi:10.1158/1538-7445.AM2013-4809

Nutrient-based dietary patterns and pancreatic cancer risk

PurposeFew data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. MethodsCases were 326 incident pancreatic cancer cases and controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. ResultsWe identified four dietary patterns—named “animal products,” “unsaturated fats,” “vitamins and fiber,” and “starch rich,” that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29–3.19) and 1.69 (95% CI, 1.02–2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35–0.86), whereas no association was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71–1.78). ConclusionsA diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated.

Smoking and other risk factors for pancreatic cancer: A cohort study in men in Lithuania

Background: Cancer of the pancreas is a relatively rare, but highly fatal cancer worldwide. Cigarette smoking has been recognized as an important risk factor, but the relation to other potential determinants is still inconsistent. We investigated the association between different lifestyle, biological and anthropometric factors and the risk of pancreatic cancer in a prospective population-based cohort study from Kaunas, Lithuania. Methods: Our study included 7132 urban men initially free from any diagnosed cancer, followed for up to 30 years. 77 incident cases of pancreatic cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Compared to never smokers, current smokers had a significantly increased risk of pancreatic cancer, HR was 1.79 (95% CI 1.03–3.09) after adjustment for age, body mass index, education and alcohol consumption. Among smokers, a significant association with higher smoking intensity was shown (≥20cigarettes/day: HR=2.60; 95% CI 1.42–4.76, Ptrend=0.046). We also observed a significantly increased risk for ≥30 pack-years of smoking (HR=2.24; 95% CI 1.12–4.49, Ptrend=0.16) and for age at starting smoking <18 years (HR=2.29; 95% CI 1.11–4.70, Ptrend=0.43) as compared to never smokers. Alcohol consumption, body mass index and total cholesterol level were not significantly associated with pancreatic cancer. Conclusions: Smoking significantly increases pancreatic cancer incidence and its high prevalence in Lithuania may partly explain high incidence of the disease. No convincing evidence was found that alcohol consumption, body mass index or serum cholesterol level were associated with pancreatic cancer risk, although the assessment was limited by the lack of statistical power.

The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers

Background:Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation.Methods:We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases.Results:Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03–5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36–7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family.Conclusion:The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies.

Abstract 625: Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Abstract Flavonoids are the most common of the plant polyphenolics and are obtained from foods such as tea, citrus and other fruits. Laboratory and animal studies suggest that through anti-oxidant properties dietary flavonoids may reduce the risk of pancreatic cancer, and the few previous epidemiologic studies on flavonoid intake and pancreatic cancer risk have shown protective associations for specific types of flavonoids. We examined the association between total flavonoid intake, six flavonoid subgroups, flavonoid-rich foods and development of exocrine pancreatic cancer among 537,104 participants in the NIH-AARP Diet and Health Study with complete dietary data. Men and women aged 50 to 71 years completed a self-administered food frequency questionnaire at baseline (1995-1996) that ascertained diet and other lifestyle information. During follow-up through 2006 (median 10.6 years, max 11.2 years), 2379 incident pancreatic cancer cases were identified. Flavonoid intake was estimated from two databases developed from the USDA Nutrient Data laboratory. The distribution of flavonoid intake differed by sex (mean female intake 216 mg/day, range 0.41-9456; mean male intake 153 mg/day, range 0.95-6561); therefore, quintiles were based on sex specific cut-points. We used Cox proportional hazard models with age as the underlying time metric to calculate hazard ratios (HR) for pancreatic cancer. Models were adjusted for sex, smoking, diabetes, body mass index, alcohol use, and saturated fat and red meat intake. We found no association between total flavonoid intake (hazard ratio (HR)=1.09; 95% confidence interval (CI) 0.96-1.24) or the six flavonoid subgroups and risk of pancreatic cancer. Although there was no significant interaction by sex or smoking (p-interaction &amp;gt; 0.10), in stratified analyses we observed significant increased risks for total flavonoid intake among current smokers (Q5 versus Q1 HR=1.45, 95% CI 1.12-1.88, p-trend=0.002), while no such associations were evident among never (HR=1.01, 95% CI 1.00-1.03) or former smokers (HR=0.99, 95% CI 0.98-1.01). Among smokers flavonol and isoflavone intakes were positively associated with pancreatic cancer comparing extreme quintiles, with HRs =1.38 (95% CI 1.05-1.82, p trend=0.019) and 1.39 (95% CI 1.03-1.86, p trend=0.022) respectively. It is possible that exposures correlated to smoking but not accounted for in our analysis explain the observed associations. Our results do not support the hypothesis that flavonoid intake plays a protective role in pancreatic cancer carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 625. doi:1538-7445.AM2012-625

Coffee, Tea, and Sugar-Sweetened Carbonated Soft Drink Intake and Pancreatic Cancer Risk: A Pooled Analysis of 14 Cohort Studies

Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

Identifying patients with suspected pancreatic cancer in primary care: derivation and validation of an algorithm

Pancreatic cancer has the worst survival for any cancer and is often diagnosed late when the cancer is advanced. Chances of survival are more likely if patients can be diagnosed earlier. To derive and validate an algorithm to estimate absolute risk of having pancreatic cancer in patients with and without symptoms in primary care. Cohort study using data from 375 UK QResearch® general practices for development and 189 for validation. Included patients were aged 30-84 years, free at baseline from a diagnosis of pancreatic cancer and had not had dysphagia, abdominal pain, abdominal distension, appetite loss, or weight loss recorded in the preceding 12 months. The primary outcome was incident diagnosis of pancreatic cancer recorded in the following 2 years. Risk factors examined included: age, body mass index, smoking status, alcohol, deprivation, diabetes, pancreatitis, previous diagnosis of cancer apart from pancreatic cancer, dysphagia, abdominal pain, abdominal distension, appetite loss, weight loss, diarrhoea, constipation, tiredness, itching, and anaemia. Cox proportional hazards models were used to develop separate risk equations in males and females. Measures of calibration and discrimination assessed performance in the validation cohort. There were a total of 1415 incident cases of pancreatic cancer from 4.1 million person-years in the derivation cohort. Independent predictors in both males and females were age, smoking, type 2 diabetes, chronic pancreatitis, abdominal pain, appetite loss, and weight loss. Abdominal distension was a predictor for females only; dysphagia and constipation were predictors for males only. On validation, the algorithms explained 59% of the variation in females and 62% in males. The receiver operating characteristic statistics were 0.84 (females) and 0.87 (males). The D statistic was 2.44 (females) and 2.61 (males). The 10% of patients with the highest predicted risks contained 62% of all pancreatic cancers diagnosed over the following 2 years. The algorithm has good discrimination and calibration and could potentially be used to help identify those at highest risk of pancreatic cancer to facilitate early referral and investigation.

Comparison of adiponectin concentration between pancreatic cancer and colorectal cancer.

Adiponectin (ADP) is an adipocytokine secreted by the adipose tissue which can be a useful marker in oncogenesis. Preliminary studies suggest that adiponectin rates differ according to the type of cancer. Compare ADP plasma levels in pancreatic cancer (PC) and colorectal cancer (CRC) in a prospective monocentric study. The study included all the incident cases of PC gathered from a university hospital in France from January 2006 till September 2007. A control population of incident cases of colorectal cancer (CRC), matching on age, gender, and tumor staging was set in the same period. In addition to demographic data, the other parameters analyzed were: ADP rate, insulinoresistance (Homa-test), presence of a dysmetabolic syndrome, evolution of weight and data concerning the tumor (staging, tumor markers: ACE, CA19.9). 33 CRC and 53 PC were analyzed. Type 2 diabetes was found in 18.2% of the CRC cases and 39.6% of the PC (p = 0.037). The mean ADP level was significantly higher in PC versus CRC (20.9 microgram/l versus 15.9 microgram/l; p = 0.03). In multivariate analysis , after adjusting for gender, age, bilirubinemia and weigth loss, the variables independently associated with a high level of ADP (> 10 microG/L) were type 2 diabetes (OR = 0.05, p = 0.01), insulinoresistance (OR = 0.42, p = 0.05) and PC (OR = 12.03, p = 0.047). ADP concentration is higher in PC patients than in CRC patients. ADP concentration > 10 microgram/l was independently associated with pancreatic cancer. Our data confirm that adiponectin rates differ strongly according to the type of cancer.