Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium.

BACKGROUND: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. METHODS: We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. RESULTS: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. CONCLUSIONS: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. IMPACT: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.

SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10⁻5) and rs828054 (OR = 1.06; p = 1 × 10⁻4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10⁻6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case-control study.

PURPOSE: Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results. METHODS: We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods. RESULTS: Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39-0.84; OR = 0.64, 95 % CI: 0.44-0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71-0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45-0.88). CONCLUSIONS: Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.

Green tea drinking and risk of pancreatic cancer: a large-scale, population-based case-control study in urban Shanghai.

BACKGROUND: Little is known about the etiology of pancreatic cancer. Epidemiological studies on tea consumption and pancreatic cancer risk have been inconclusive. The purpose of the present study was to investigate the association between green tea drinking and the risk of pancreatic cancer in urban Shanghai, China. METHODS: In this population-based case-control study conducted in urban Shanghai, 908 cases of pancreatic cancer and 1067 healthy controls were recruited. Information on tea drinking, including type of tea, amount of tea consumption, temperature of tea, and the duration of regular tea drinking, were collected via interview questionnaire. RESULTS: We examined the association of multiple tea drinking habits with the risk of pancreatic cancer. In women, regular green tea drinking was associated with 32% reduction of pancreatic cancer risk (OR 0.68, 95% CI 0.48-0.96), compared to those who did not drink tea regularly. Increased consumption and longer duration of tea drinking were both associated with reduced pancreatic cancer risk in women. Among regular tea drinkers, lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, independent of amount or duration of tea drinking. CONCLUSIONS: Habits of green tea drinking, including regular drinking, amount of consumption, persistence of the habit, and tea temperature, may lower pancreatic cancer risk.