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.

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.

Omega-3 and -6 Fatty Acid Intake and Colorectal Cancer Risk in Swedish Women's Lifestyle and Health Cohort.

PURPOSE: We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women. MATERIALS AND METHODS: A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers. RESULTS: During a median of 21.3 years of follow-up, a total of 344 colorectal cancer cases were ascertained. Although there was no overall association between omega-3 fatty acid intake and colorectal cancer risk, high intake of fish-derived docosahexaenoic acid was associated with reduced risk of rectal cancer (hazard ratios for the third and the highest quartiles were 0.59 (95% confidence interval [CI], 0.37 to 0.96) and 0.62 (95% CI, 0.39 to 0.98), respectively). CONCLUSION: In conclusion, we found only limited support for an association between omega-3 polyunsaturated fatty acids and colorectal cancer in a large Swedish cohort of middle-aged women.

Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring.

Importance: The association of maternal use of folic acid and multivitamin supplements before and during pregnancy with the risk of autism spectrum disorder (ASD) in offspring is unclear. Objective: To examine the associations between the use of maternal folic acid and multivitamin supplements before and during pregnancy and the risk of ASD in offspring. Design, Setting, and Participants: A case-control cohort study of 45 300 Israeli children born between January 1, 2003, and December 31, 2007, were followed up from birth to January 26, 2015, for the risk of ASD. The cases were all children diagnosed with ASD and the controls were a random sample of 33% of all live-born children. Exposures: Maternal vitamin supplements were classified for folic acid (vitamin B9), multivitamin supplements (Anatomical Therapeutic Chemical A11 codes vitamins A, B, C, and D), and any combination thereof exposed in the intervals before and during pregnancy. Main Outcomes and Measures: The association between maternal vitamin supplementation and the risk of ASD in offspring was quantified with relative risks (RRs) and their 95% CIs fitting Cox proportional hazards regression models adjusted for confounders. Sensitivity analyses were performed to test the robustness of the results. Results: Of the 45 300 children in the study (22 090 girls and 23 210 boys; mean [SD] age, 10.0 [1.4] years at the end of follow-up), 572 (1.3%) received a diagnosis of ASD. Maternal exposure to folic acid and/or multivitamin supplements before pregnancy was statistically significantly associated with a lower likelihood of ASD in the offspring compared with no exposure before pregnancy (RR, 0.39; 95% CI, 0.30-0.50; P < .001). Maternal exposure to folic acid and/or multivitamin supplements during pregnancy was statistically significantly associated with a lower likelihood of ASD in offspring compared with no exposure during pregnancy (RR, 0.27; 95% CI, 0.22-0.33; P < .001). Corresponding RRs were estimated for maternal exposure to folic acid before pregnancy (RR, 0.56; 95% CI, 0.42-0.74; P = .001), maternal exposure to folic acid during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P < .001), maternal exposure to multivitamin supplements before pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P < .001), and maternal exposure to multivitamin supplements during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P < .001). The results generally remained statistically significant across sensitivity analyses. Conclusions and Relevance: Maternal exposure to folic acid and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASD in the offspring compared with the offspring of mothers without such exposure.

Prospective Study of Dietary Phytoestrogen Intake and the Risk of Colorectal Cancer.

Dietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer. We evaluated the associations between dietary lignan intake, dietary isoflavonoid intake, dietary coumestrol intake, and dietary enterolignans and equol intake, and risk of colorectal cancer. Data from the Women's Lifestyle and Health (WLH) Cohort study was used. The WLH study is a prospective population-based cohort study including 48,268 Swedish women aged 30-49 years at the time of enrolment in 1991-92. Follow-up for colorectal cancer incidence, death, and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register. During follow-up 206 incident colorectal cancer cases were identified. Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95% confidence intervals. We found no statistically significant association between the intake of dietary lignans, dietary isoflavonoids, coumestrol, or enterolignans and equol, and risk of colorectal cancer. We found no association between dietary phytoestrogen intake and the risk of colorectal cancer. However, since the number of cancer cases was small, our results need to be confirmed. Future studies should investigate colon and rectal cancer separately.

Prospective study of coffee consumption and all-cause, cancer, and cardiovascular mortality in Swedish women.

We investigated whether coffee consumption was associated with all-cause, cancer, or cardiovascular mortality in a prospective cohort of 49,259 Swedish women. Of the 1576 deaths that occurred in the cohort, 956 were due to cancer and 158 were due to cardiovascular disease. We used Cox proportional hazard models with adjustment for potential confounders to estimate multivariable relative risks (RR) and 95 % confidence intervals (CI). Compared to a coffee consumption of 0-1 cups/day, the RR for all cause-mortality was 0.81 (95 % CI 0.69-0.94) for 2-5 cups/day and 0.88 (95 % CI 0.74-1.05) for >5 cups/day. Coffee consumption was not associated with cancer mortality or cardiovascular mortality when analyzed in the entire cohort. However, in supplementary analyses of women over 50 years of age, the RR for all cause-mortality was 0.74 (95 % CI 0.62-0.89) for 2-5 cups/day and 0.86 (95 % CI 0.70-1.06) for >5 cups/day when compared to 0-1 cups/day. In this same subgroup, the RRs for cancer mortality were 1.06 (95 % CI 0.81-1.38) for 2-5 cups/day and 1.40 (95 % CI 1.05-1.89) for >5 cups/day when compared to 0-1 cups/day. No associations between coffee consumption and all-cause mortality, cancer mortality, or cardiovascular mortality were observed among women below 50 years of age. In conclusion, higher coffee consumption was associated with lower all-cause mortality when compared to a consumption of 0-1 cups/day. Furthermore, coffee may have differential effects on mortality before and after 50 years of age.

Prospective study of breast cancer in relation to coffee, tea and caffeine in Sweden.

Studies of coffee and tea consumption and caffeine intake as risk factors for breast cancer are inconclusive. We assessed coffee and tea consumption, caffeine intake, and possible confounding factors among 42,099 women from the Swedish Women's Lifestyle and Health study, the participants of which were aged 30-49 years at enrollment in 1991-1992. Complete follow-up for breast cancer incidence was performed through 2012 via linkage to national registries. Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer. During follow-up 1,395 breast cancers were diagnosed. The RR was 0.97 (95% CI 0.94-0.99) for a 1-unit increase in cups of coffee/day, 1.14 (95% CI 1.05-1.24) for a 1-unit increase in cups of tea/day, and 0.97 (95% CI 0.95-1.00) for a 100 mg/day increase in caffeine intake. Although the RR for no consumption (RR = 0.86, 95% CI 0.69-1.08), a group with a relatively small number of women, was not statistically significant, women with higher consumption had a decreased breast cancer risk (3-4 cups/day: RR = 0.87, 95% CI 0.76-1.00; ≥5 cups/day: RR = 0.81, 95% CI 0.70-0.94) compared to women consuming 1-2 cups of coffee/day. Compared to no consumption, women consuming >1 cups tea/day showed an increased breast cancer risk (RR = 1.19, 95% CI 1.00-1.42). Similar patterns of estimates were observed for breast cancer risk overall, during pre- and postmenopausal years, and for ER+ or PR+ breast cancer, but not for ER- and PR- breast cancer. Our findings suggest that coffee consumption and caffeine intake is negatively associated with the risk of overall and ER+/PR- breast cancer, and tea consumption is positively associated with the risk of overall and ER+/PR+ breast cancer.

Endometrial cancer in relation to coffee, tea, and caffeine consumption: a prospective cohort study among middle-aged women in Sweden.

This study aimed to add to prospective data on the possible inverse association between coffee consumption and endometrial cancer risk, already supported by several case-control studies. Coffee and tea consumption and possible confounding factors were assessed among 42,270 women aged 30-49 years at enrollment in 1991-1992 in the Swedish Women's Lifestyle and Health cohort study, with complete follow-up through 2009. We calculated caffeine intake per day; Cox proportional hazard models were used to estimate multivariable relative risks (mRR) for endometrial cancer with 95% confidence intervals (CIs). One hundred forty-four endometrial cancers were diagnosed during follow-up. Women with and without endometrial cancer had a similar mean daily coffee consumption (549 vs. 547 g), tea consumption (104 vs. 115 g), and caffeine intake (405 vs. 406 mg). Compared to those consuming <2 cups of coffee per day, women consuming >3 cups had a mRR of 1.56 (95% CI: 0.94-2.59; P for trend = 0.17). Compared with the lowest tertile of caffeine intake, the highest tertile had a mRR of 1.32 (95% CI: 0.87-1.99; P for trend = 0.27). Our study provides no convincing evidence of an association between coffee consumption, tea consumption, or caffeine intake and endometrial cancer risk among middle-aged women.

Prospective study of solar exposure, dietary vitamin D intake, and risk of breast cancer among middle-aged women.

The relationship between solar exposure or dietary vitamin D intake and breast cancer risk has not been fully elucidated. These associations were studied within the Women's Lifestyle and Health Cohort Study, a cohort of 49,259 Swedish women ages 30 to 50 years at baseline (1991-1992). Women were asked about solar exposure and completed a food frequency questionnaire and were followed-up through linkages to national registries until December 2004. In the current analyses, 41,889 women were included, 840 of whom were diagnosed with breast cancer during follow-up. Breast cancer risk was not related to solar exposure variables, including sun sensitivity, annual number of sunburns, time spent on sunbathing vacations, or solarium use at any age period of exposure. There was also no association with dietary vitamin D intake or supplementary multivitamin use. These relationships were not modified after stratifying by estrogen or progesterone receptor status.

Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women.

Results from epidemiological and experimental studies indicate that phytoestrogens may protect against breast cancer. Because one of the biological effects of phytoestrogens is probably estrogenic, it's possible that the preventive effect on breast cancer differs by estrogen receptor (ER) or progesterone receptor (PR) status of the tumor. We evaluated the associations between dietary phytoestrogen (isoflavonoids, lignans, and coumestrol) intake and risk of breast cancer and whether the ER/PR statuses of the tumor influence this relationship. In 1991-2 a prospective population-based cohort study among Swedish pre- and postmenopausal women was performed, making questionnaire data available for 45,448 women. A total of 1014 invasive breast cancers were diagnosed until December 2004. Cox proportional hazards models were performed to estimate multivariate risk ratios, 95% CI for associations with risk of breast cancer. Intakes of lignan, isoflavonoid, or coumestrol were not associated with breast cancer risk overall or before or after 50 y of age. The effects of lignans or isoflavonoids were independent of receptor status. However, intake of coumestrol was associated with decreased risk of receptor negative tumors (ER-PR-) but not positive tumors. The risk of ER-PR- tumors was significantly lower (50%) in women with intermediate coumestrol intake compared with those who did not consume any. In conclusion, we found no association between intake of isoflavonoids or lignans and breast cancer risk. Our results of a decreased risk of ER-PR- tumors in women with intermediate intake of coumestrol could be due to chance because of the low intake. The results should be confirmed in other studies.