Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study.

OBJECTIVE: To assess the relationships between female hormonal exposures and risk of RA in a prospective cohort of French women. METHODS: E3N (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale) is an on-going French prospective cohort that included 98 995 women aged 40-65 years in 1990. Every 2-3 years, women completed mailed questionnaires on their lifestyles, reproductive factors and health conditions. Cox proportional hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% CIs were estimated. Effect modification by smoking history was investigated. RESULTS: A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95% CI 1.0, 1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95% CI 1.0, 1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95% CI 1.0, 2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95% CI 0.2, 0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (>24 vs 0 months; multi-adjusted HR = 0.77; 95% CI 0.6, 0.9). CONCLUSIONS: These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort.

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925-1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05-4.69]; 4th quartile: OR = 2.33 [CI = 1.11-4.90]); Ptrend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07-5.65]; 4th quartile: OR = 2.76 [CI = 1.21-6.30]; Ptrend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER-: OR = 15.40 [CI = 1.84-129.19]; PR-: OR = 3.47 [CI = 1.29-9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR = 7.73 [CI = 1.46-41.08]; PR-: OR = 3.44 [CI = 1.30-9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.

Mediterranean Diet and Risk of Rheumatoid Arthritis: Findings From the French E3N-EPIC Cohort Study.

OBJECTIVE: The Mediterranean diet has been reported to be associated with a significant reduction in risk of noncommunicable diseases. We undertook this study to assess the relationship between adherence to the Mediterranean diet and the risk of rheumatoid arthritis (RA), especially in high-risk individuals. METHODS: The E3N study (Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l'Education Nationale) is a French prospective cohort study that has included 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to the Mediterranean diet was assessed using a 9-unit dietary score evaluating consumption of vegetables, legumes, cereal products, fish, meat, dairy products, olive oil, and alcohol. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident RA were estimated using Cox proportional hazards regression models adjusted for age and the main potential confounders, including smoking. RESULTS: Among 62,629 women, we identified 480 incident cases of RA. In the entire study population, the Mediterranean diet adherence score was not associated with RA risk (HR 0.86 [95% CI 0.67-1.09] for high score versus low score; P for trend = 0.09); however, among ever-smokers, a higher score was associated with a decreased risk of RA (HR 0.91 [95% CI 0.84-0.99] for 1-point increase in score; P = 0.03). In ever-smokers, the absolute risks of RA in those with high scores and those with low scores were 38.3 and 51.5 per 100,000 person-years, respectively, compared to 35.8 per 100,000 person-years in never-smokers with high Mediterranean diet scores. CONCLUSION: Our results suggest that adherence to the Mediterranean diet could reduce the high risk of RA among ever-smoking women. Our results must be confirmed in future research.

Dietary exposure to brominated flame retardants and risk of type 2 diabetes in the French E3N cohort.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) is increasing worldwide. Recent studies have suggested that environmental factors, such as exposure to brominated flame retardants (BFRs), could play a role in the epidemic of T2D. The aim of this study was to analyze the association between the dietary exposure to BFRs (Hexabromocyclododecane (HBCD) and Polybromodiphenylether (PBDE)) and T2D risk in the E3N prospective cohort of French women. RESEARCH DESIGN AND METHODS: Overall, 71,415 women followed for 19 years were included in the study. We performed Cox regression models to analyze the association between dietary exposure to BFRs and T2D risk. RESULTS: Overall 71,415 women were included and 3667 (5.13%) developed a T2D during follow-up. The mean dietary exposure to HBCD and to PBDE was 0.22 ng/kg body weight (BW)/day and 1.21 ng/kg bw/day, respectively. There was a positive linear association between dietary exposure to HBCD and T2D risk starting from the 2nd quintile group (HR: 1.18; 95% CI: 1.06-1.30) to the 5th quintile group (HR: 1.47; 95% CI: 1.29-1.67) when compared to the 1st quintile group. We also found positive although non-linear associations between dietary exposure to PBDE and T2D risk, with an increased HR only for the 2nd and 4th vs. 1st quintile groups (HR: 1.12; 95% CI: 1.02-1.24, and HR: 1.20; 95% CI: 1.08-1.34, respectively). CONCLUSION: The findings suggest an association between dietary exposure to BFRs and T2D risk, highlighting the importance of further investigating this association the long-term health effects of endocrine disruptors in the general population. Additional studies are needed to reproduce these findings in other populations and clarify the underlying biological mechanisms.

Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections.

Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.