Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population-based case-control study in the San Francisco Bay area.

OBJECTIVE: The aim of this study was to evaluate a complex association among intake of dietary vitamin D, calcium, and retinol, and pancreatic cancer risk. METHODS: Pancreatic cancer cases (n = 532) diagnosed in 1995-1999 were identified using rapid case ascertainment methods and were frequency matched to population-based controls (n = 1,701) in the San Francisco Bay Area. Detailed dietary data were collected during in-person interviews using a validated semi-quantitative food-frequency questionnaire. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and confidence intervals. RESULTS: In men, increased pancreatic cancer risk was associated with currently recommended dietary vitamin D intake levels (highest (≥450 IU/day) vs. lowest (<150 IU/day) intake, OR = 2.6, trend-p = 0.009) and total vitamin D intake from diet and supplements (for <800 IU/day). ORs for dietary vitamin D intake remained increased after adjustment for intake of retinol and calcium, although confidence intervals included unity. Stratified analyses showed that ORs were higher among men with lower intake of retinol and lower physical activity but there was no evidence of statistical interaction. No associations with vitamin D intake were observed among women, although ORs typically were elevated. ORs increased with increased dietary calcium intake among men (trend-p = 0.008) and not women. CONCLUSIONS: Our results among men showing an increased risk of pancreatic cancer associated with dietary intake of vitamin D and of calcium require confirmation in further studies. Continued investigation is needed to clarify the complex role of vitamin D and calcium in pancreatic cancer risk and to determine their optimal intake level and preventive effects for pancreatic cancer.

Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.

There are no well-established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p(trend) < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2-2.1) and 1.4 (95% CI: 1.1-1.9); both p(trend) < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1-2.0); p(trend) = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50-0.92); p(trend) = 0.007] and omega-3 fatty acids [>or=0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25-0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51-0.94); p(trend) = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49-0.92); p(trend) = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p(trend) < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk.

Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study.

OBJECTIVE: Folate and other methyl-group nutrients may play a key role in pancreatic carcinogenesis through their effects on DNA integrity. We examined the association between pancreatic cancer and intake of folate, vitamins B(6), B(12) and methionine in a large population-based case-control study. METHODS: Risk factor data were collected during in-person interviews with 532 pancreatic cancer cases diagnosed in 1995-1999 and 1,701 frequency-matched controls in the San Francisco Bay Area. Dietary history and supplement use were obtained using a semi-quantitative food-frequency questionnaire developed at Harvard University. Adjusted unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) as estimates of the relative risk. RESULTS: Total folate intake was inversely associated with pancreatic cancer (5th vs. 1st quintile: OR = 0.67, 95% CI = 0.48-0.93, p (trend) = 0.04). Increased vitamin B(12) from food was positively associated with pancreatic cancer although risk estimates for quintiles 3-5 were similar (5th vs. 1st quintile: OR = 1.9, 95% CI = 1.3-2.6, p (trend) = 0.001). Intake of vitamin B(6) or methionine was not associated with pancreatic cancer risk. CONCLUSIONS: Our study provided some support for an inverse association between folate intake and pancreatic cancer risk. The increased pancreatic cancer risk with vitamin B(12) intake from food warrants further investigation.

Diet and melanoma in a case-control study.

BACKGROUND: Malignant melanoma has been one of the most rapidly increasing cancers within the United States with few modifiable risk factors. This study investigates risk related to dietary factors, which are potentially modifiable. METHODS: Newly diagnosed patients with melanoma (n = 502) were recruited from pigment lesion clinics and controls (n = 565) were recruited from outpatient clinics. To investigate the relationship between melanoma and dietary factors in this case-control study, study subjects were requested to complete a food frequency questionnaire, which assessed diet over the previous year. Using logistic regression, odds ratios (ORs) for melanoma were computed for nutrient and alcohol intake. RESULTS: Persons in high versus low quintiles of energy-adjusted vitamin D, alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene had significantly reduced risk for melanoma (ORs < or = 0.67), which remained after adjustment for presence of dysplastic nevi, education, and skin response to repeated sun exposure. Addition of micronutrients from supplements did not add an additional reduction in risk. High alcohol consumption was associated with an increased risk for melanoma, which remained after adjustment for confounders [OR (95% confidence interval) in highest versus lowest quintiles, 1.65 (1.09-2.49)]. CONCLUSIONS: Diets consisting of foods rich in vitamin D and carotenoids and low in alcohol may be associated with a reduction in risk for melanoma. These analyses should be repeated in large, prospective studies.