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.

Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND: The etiology of mantle cell lymphoma (MCL), a distinctive subtype accounting for 2%-10% of all non-Hodgkin lymphoma, is not known. METHODS: We investigated associations with self-reported medical history, lifestyle, family history, and occupational risk factors in a pooled analysis of 557 patients with MCL and 13766 controls from 13 case-control studies in Europe, North America, and Australia. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each exposure were examined using multivariate logistic regression models. RESULTS: The median age of the MCL patients was 62 years and 76% were men. Risk of MCL was inversely associated with history of hay fever (OR = 0.63, 95% CI = 0.48 to 0.82), and the association was independent of other atopic diseases and allergies. A hematological malignancy among first-degree relatives was associated with a twofold increased risk of MCL (OR = 1.99, 95% CI = 1.39 to 2.84), which was stronger in men (OR = 2.21, 95% CI = 1.44 to 3.38) than women (OR = 1.61, 95% CI = 0.82 to 3.19). A modestly increased risk of MCL was also observed in association with ever having lived on a farm (OR = 1.40, 95% CI = 1.03 to 1.90). Unlike some other non-Hodgkin lymphoma subtypes, MCL risk was not statistically significantly associated with autoimmune disorders, tobacco smoking, alcohol intake, body mass index, or ultraviolet radiation. CONCLUSIONS: The novel observations of a possible role for atopy and allergy and farm life in risk of MCL, together with confirmatory evidence of a familial link, suggest a multifactorial etiology of immune-related environmental exposures and genetic susceptibility. These findings provide guidance for future research in MCL etiology.

Intake of vitamins D and A and calcium and risk of non-Hodgkin lymphoma: San Francisco Bay Area population-based case-control study.

Several nutrients identified as potentially cancer protective have been inconsistently associated with non-Hodgkin lymphoma (NHL) risk. Dietary history data, including use of vitamin supplements, were collected using a semiquantitative food frequency questionnaire administered during in-person interviews with 4,133 participants (2,052 cases, 2,081 controls) in a San Francisco Bay Area population-based case-control study. Data were used to determine the association of intake levels of vitamins D and A and calcium with risk of NHL and NHL subtypes. Odds ratios (OR) and 95% confidence intervals (CI) were computed as estimates of relative risk using adjusted unconditional logistic regression. Increasing vitamin D intake from food and supplements was positively associated with NHL risk in men (5th quintile: OR = 1.6, 95% CI = 1.0-2.4, P(trend) = 0.07) and with diffuse large B-cell lymphoma (DLBCL) in women and men (5th quintile: OR = 1.6, 95% CI = 1.0-2.5, P(trend) = 0.02); that was largely due to the effect in men (P(trend) = 0.03). These results do not support a strong role for vitamin D intake with NHL risk, with the exception of a potential association for DLBCL risk in men. Our results should be interpreted conservatively until further investigation in larger pooled studies can be conducted to better assess the role of vitamin D intake in lymphomagenesis.

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.