Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort.

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged >50 y: a prospective study.

BACKGROUND: Soy-based dietary supplements have been promoted as natural alternatives to menopausal hormone therapy, but their potential effect on breast cancer development is controversial. OBJECTIVES: We examined the relation between the consumption of soy supplements and the risk of breast cancer, overall and by tumor hormone receptor status, among women aged >50 y. METHODS: In total, 76,442 women from the Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) cohort, born between 1925 and 1950, were followed from 2000 to 2011 (11.2 y on average, starting at a mean age of 59.5 y; 3608 incident breast cancers), with soy supplement use assessed every 2-3 y. HRs of breast cancer were estimated with the use of multivariable Cox models. RESULTS: Compared with never using soy supplements, the HRs associated with current use of soy supplements were 0.92 (95% CI: 0.76, 1.11) for all, 0.78 (95% CI: 0.60, 0.99) for estrogen receptor (ER)-positive, and 2.01 (95% CI: 1.41, 2.86) for ER-negative breast cancers. There was no association between past use of soy supplements and breast cancer. HRs for current use were 1.36 (95% CI: 0.95, 1.93) and 0.82 (95% CI: 0.65, 1.02) among women with and without a family history of breast cancer, respectively (P-interaction = 0.03) and 1.06 (95% CI: 0.87, 1.30) ≥5 y after menopause compared with 0.50 (95% CI: 0.31, 0.81) in premenopause or ≤5 y postmenopause (P-interaction = 0.04). CONCLUSIONS: In this cohort of women aged >50 y, we report opposing associations of soy supplements with ER-positive and ER-negative breast cancer risk. Our results also caution against the use of these supplements in women with a family history of breast cancer. Whether the risk profile of soy supplements could be more favorable among premenopausal or recently postmenopausal women deserves further investigation.

Comparison of chlordecone and NDL-PCB decontamination dynamics in growing male kids after cessation of oral exposure: Is there a potential to decrease the body levels of these pollutants by dietary supplementation of activated carbon or paraffin oil?

Sixteen weaned male Alpine kids (Capra hircus) were subjected to a 21-day oral daily exposure of 0.05 mg kg-1 BW. d-1 of chlordecone (CLD) and 0.30 µg kg-1 BW. d-1 of each non-dioxin-like polychlorinated biphenyls (NDL-PCBs, congeners 28, 52, 101, 138, 153 and 180). Four kids, identified as the CONTA group, were slaughtered at the end of the exposure, while the remaining animals (n = 12) were fed with specific diets for an additional 21-day decontamination period before slaughtering. Kids from the DECONTA (n = 4) group were fed a control diet, while those from the AC10% and PO8% group received pellets supplemented with 10% activated carbon (AC) and 8% paraffin oil (PO), respectively. CLD and NDL-PCB levels in blood, liver, peri-renal fat and muscles from different groups were analysed to compare the decontamination dynamics of the pollutants and to determine the efficiency of AC and PO to decrease the body levels of pollutants. After the decontamination period, the CLD levels considerably decreased (more than 60%) in blood, liver, muscles and fat. Concerning NDL-PCBs, the decontamination process was much lower. Overall, CLD appeared to be less retained in kids' organism compared with NDL-PCBs, and the decontamination dynamics of these pollutants appeared to be different because of their specific physicochemical properties and lipophilicity. Furthermore, the dietary supplementation with AC or PO did not significantly affect the decontamination dynamics.

Activated carbon, a useful medium to bind chlordecone in soil and limit its transfer to growing goat kids.

Chlordecone (Kepone) (CLD) is a highly persistent pesticide which was extensively used in the French West Indies; high levels of CLD can still currently be found in large agricultural areas. As CLD transfers from soil to animals mainly via involuntary ingestion, the consumption of foodstuffs derived from animals raised in contaminated areas may significantly contribute to exposure of humans to CLD. The present study was designed to test the efficacy of two different activated carbons (ACs) sources in limiting CLD transfer from soil to animal. Three soils (ASs) were prepared according to the OECD guideline 207. One standard soil (SS) lacking AC, and two modified preparations of SS supplemented with 2% coconut-based activated carbon (ORBO), SSO or with 2% lignite-based one (DARCO), SSD. All three soils were spiked with 10 µg of kepone per g of dry matter and aged for three weeks. This study involved 15 goat kids randomly assigned to the 3 experimental groups (n = 5/group), which were fed the experimental matrices at an exposure dose of 10 µg CLD per kg of body weight per day. After 21 d of oral exposure, CLD in adipose tissue and liver were analysed by LC-MS-MS. A significant decrease of 63.7% and 74.7% of CLD concentrations in adipose tissue and liver, respectively, were obtained from animals exposed using SS containing DARCO as compared to those receiving only SS. Decreases in CLD levels of 98.2% (adipose tissue) and 98.7% (liver) were obtained for animals exposed using SS containing ORBO. This study leads us to conclude that (i) the presence of AC in CLD-contaminated soil strongly reduces CLD bioavailability, and (ii) the efficacy depends on the nature and characteristics of the AC used.

Use of Bisphosphonates and Risk of Breast Cancer in a French Cohort of Postmenopausal Women.

Purpose To assess whether bisphosphonate (BP) use is associated with decreased breast cancer incidence in a cohort of postmenopausal women. Methods The study population included 64,438 postmenopausal women participating in the French E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) prospective cohort, with data self-reported in biennial questionnaires matched with data from a drug reimbursement database. Exposure to BPs and the use of other osteoporosis treatments during follow-up were determined using reimbursement data. Other covariates (breast cancer risk factors, clinical risk factors for osteoporotic fractures, and bone mineral density surveillance) originated from the questionnaires. Hazard ratios (HRs) of breast cancer were estimated using Cox proportional hazards models, considering exposure as a time-varying variable. Results Over an average of 7.2 years of follow-up (2004 to 2011), 2,407 first primary breast cancer cases were identified. The HR of breast cancer associated with exposure to BPs was 0.98 (95% CI, 0.85 to 1.12). We found no effect modification by age, body mass index, time since menopause, use of hormone replacement therapy, use of calcium supplements, or use of vitamin D supplements. There was no heterogeneity across BP molecules and no trend according to cumulative dose, duration of use, or time since last use. We observed a decrease in breast cancer risk restricted to the year after treatment initiation (HR, 0.56; 95% CI, 0.36 to 0.87), which was likely explained by healthy screenee bias. Finally, we did not find any variation in HRs across breast carcinomas defined by their estrogen receptor or invasive or in situ status. Conclusion In our observational cohort of postmenopausal women observed from 2004 to 2011, BP use, likely prescribed for the management of osteoporosis, was not associated with decreased breast cancer incidence.

Postmenopausal breast cancer risk and interactions between body mass index, menopausal hormone therapy use, and vitamin D supplementation: Evidence from the E3N cohort.

Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, but epidemiological evidence is not conclusive. Body mass index (BMI) has been shown to modulate the effect of supplementation on the vitamin D status, but its potential influence on the relationship with breast cancer risk has been little studied. We investigated a potential interaction between BMI and vitamin D supplementation on breast cancer risk while considering an already reported interaction between vitamin D supplementation and menopausal hormone therapy (MHT) use. Vitamin D supplementation was prospectively investigated in 57,403 postmenopausal women from the French E3N cohort including 2,482 incident breast cancer cases diagnosed between 1995 and 2008. Multivariable hazard ratios (HR) for primary invasive breast cancer and 95% confidence intervals (CI) were estimated using Cox models. Among MHT ever users, vitamin D supplementation was associated with decreased breast cancer risk, similarly across BMI strata (Phomogeneity = 0.83). Among MHT never users, ever vitamin D supplementation was associated with increased postmenopausal breast cancer risk in women with baseline BMI <25 kg/m(2) (HR = 1.51, 95% CI: 1.13, 2.02), but not in women with higher BMI (0.98, 95% CI: 0.62, 1.56), Phomogeneity = 0.12. In conclusion, our findings suggest that vitamin D supplementation may reduce the excess breast cancer risk in MHT users, but draw attention on a potential risk in postmenopausal women not exposed to high exogenous or endogenous hormones, i.e. non-overweight MHT-non users, especially in the present context of increasing vitamin D supplement use and decreasing MHT use.

Vitamin C supplement intake and postmenopausal breast cancer risk: interaction with dietary vitamin C.

BACKGROUND: Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk. OBJECTIVE: We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake. DESIGN: Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided. RESULTS: Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03). CONCLUSIONS: We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation.

Interaction between current vitamin D supplementation and menopausal hormone therapy use on breast cancer risk: evidence from the E3N cohort.

BACKGROUND: Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, particularly on estrogen receptor-positive tumors. Epidemiologic data are less conclusive. OBJECTIVE: Our objective was to investigate the association between postmenopausal breast cancer risk and current or past vitamin D supplementation overall and according to the use of menopausal hormone therapy (MHT). DESIGN: Between 1995 and 2008, 2482 invasive breast cancer cases were diagnosed among 57,403 postmenopausal women from the E3N prospective cohort during 581,085 person-years. Vitamin D supplementation was assessed from biennially self-administered questionnaires sent in 1995, 2000, 2002, and 2005 and from medico-administrative data on drug reimbursements since 2004. Multivariable HRs for primary invasive breast cancer and 95% CIs were estimated by using Cox models. RESULTS: A decreased postmenopausal breast cancer risk was associated with current (HR: 0.82; 95% CI: 0.69, 0.97) but not past (HR: 1.10; 95% CI: 0.92, 1.31) vitamin D supplementation (P-homogeneity = 0.02). The association with current vitamin D supplementation differed according to MHT use: ever users (HR: 0.74; 95% CI: 0.60, 0.90) and never users (HR: 1.13; 95% CI: 0.89, 1.56); P-homogeneity = 0.02. CONCLUSIONS: In this observational study, current vitamin D supplementation, mostly taken daily and combined with calcium, was associated with a decreased postmenopausal breast cancer risk in MHT users. These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk.

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition.

The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.

Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by center and age, and adjusted for body mass index, smoking, diabetes, physical activity and alcohol consumption. Compared to never use of HT at study enrollment, current use of estrogen-only (HR, 1.02; 95% CI, 0.79-1.31) or estrogen plus progestin (HR, 0.94; 95% CI, 0.77-1.14) was not significantly associated with the risk of colorectal cancer, and these associations did not vary by recency, duration, route of administration, regimen or specific constituent of HT. Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk.

Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition.

Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.

Differential dietary nutrient intake according to hormone replacement therapy use: an underestimated confounding factor in epidemiologic studies?

Observational studies and randomized controlled trials have produced divergent results concerning the effect of hormone replacement therapy (HRT) on cardiovascular disease and, to a lesser extent, dementia. Residual confounding (confounding that remains even after adjustment for various socioeconomic and lifestyle factors) is one explanation that has been offered for these divergent results. The authors used data collected between 1990 and 1995 from 6,697 French women aged 61-72 years participating in a prospective cohort study to explore the hypothesis that nutritional intake varies according to HRT use and thus may be a source of residual confounding. After the authors adjusted for health and lifestyle factors, HRT users, compared with never users, had significantly higher intakes of alcohol; omega3 fatty acids; vitamins B6, B12, and D; and phosphorus and a lower intake of starch. These differential nutrient intakes were related to differences in eating habits. In particular, HRT users in the studied sample, compared with nonusers, ate significantly more fish. Most of the dietary differences were seen in both early users and delayers of HRT. To limit residual confounding in observational studies, dietary factors may be important parameters to be taken into account in analyses of HRT use and health outcomes.