Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

Background: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. Methods and Findings: We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. Conclusions: Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms. Please see later in the article for the Editors' Summar

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

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Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: Results from the ESCAPE and TRANSPHORM projects

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Normative values for electrochemical skin conductance measurements for quantitative assessment of sudomotor function in healthy Indian adults

Context: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy. Aims: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements. Settings and Design: A sample of 217 healthy participants aged 18–75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. Statistical Analysis Used: The Shapiro–Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements. Results: The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. Conclusions: Normative values for Indians are lower than that reported for Caucasians

The association of body shape trajectories over the life course with type 2 diabetes risk in adulthood: a group-based modeling approach

International audiencePurpose - Low birth weight is a well-recognized risk factor for type 2 diabetes (T2D), but less is known about risks associated with the evolution of body shape throughout life with incident T2D in adulthood. Methods - In 80,110 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort study, trajectories of self-reported body shapes from age 8 years to 35-40 years were derived using a group-based modeling approach and studied in relation with incident T2D. Results - Compared with women who maintained a stable midrange body shape trajectory from 8 to 40 years, women in all other observed trajectories were at a higher risk of developing T2D in adulthood: The highest risk was observed for women who were lean at age 8 years and had a sharp increase in body shape (hazards ratio = 2.91 [2.35-3.62]); their T2D risk was higher (P for homogeneity = .059) than for women who maintained the largest body shape (hazards ratio = 2.18 [1.76-2.69]). Conclusions - A group-based modeling approach has identified trajectories of body shape evolution with different risks of developing T2D in adulthood. A sharp increase in body shape after puberty in previously lean girls is a risk factor for the subsequent development of diabetes

Hazard ratios and 95% confidence intervals for risk of breast cancer in relation to number of nevi, stratified by hormonal receptor status, E3N cohort (<i>n = </i>88,387).

<p>Women with missing information on hormone receptor status were excluded from this analysis (<i>n = </i>1,415).</p>b<p>Adjusted for age (timescale), education, menopausal status, age at menopause (in postmenopausal women), use of MHT (in postmenopausal women), and use of premenopausal progestogens, and stratified according to year of birth in 5-y categories (Model 2).</p>c<p>Additionally adjusted for personal history of BBD and family history of breast cancer (model used for homogeneity test) (Model 4).</p

Hazard ratios and 95% confidence intervals for risk of breast cancer in relation to number of nevi, E3N cohort (<i>n = </i>89,802).

a<p>Adjusted for age (timescale), education, menopausal status, age at menopause (in postmenopausal women), use of MHT (in postmenopausal women), and use of premenopausal progestogens, and stratified according to year of birth in 5-y categories.</p>b<p>Model 2 additionally adjusted for personal history of BBD.</p>c<p>Model 3 additionally adjusted for personal history of BBD and family history of breast cancer.</p>d<p>Model 4 additionally adjusted for BMI, height, physical activity, age at menarche, age at first full-term pregnancy, parity, breastfeeding, use of OCs, history of mammographic exam, UV dose in county of birth, and UV dose in county of residence at inclusion.</p

Hazard ratios and 95% confidence intervals for risk of breast cancer in relation to number of nevi, stratified by histological type of breast cancer, E3N cohort (<i>n</i> = 89,429).

a<p>Adjusted for age (timescale), education, menopausal status, age at menopause (in postmenopausal women), use of MHT (in postmenopausal women), and use of premenopausal progestogens, and stratified according to year of birth in 5-y categories (Model 2).</p>b<p>Additionally adjusted for personal history of BBD and family history of breast cancer (model used for homogeneity test) (Model 4).</p

Odds ratios and 95% confidence intervals for number of nevi in relation to family history of breast cancer, E3N cohort.

a<p>Adjusted for education and age at inclusion.</p

Hazard ratios and 95% confidence intervals for risk of breast cancer in relation to number of nevi, stratified by hormonal receptor status, E3N cohort (<i>n = </i>88,387).

<p>Women with missing information on hormone receptor status were excluded from this analysis (<i>n = </i>1,415).</p>b<p>Adjusted for age (timescale), education, menopausal status, age at menopause (in postmenopausal women), use of MHT (in postmenopausal women), and use of premenopausal progestogens, and stratified according to year of birth in 5-y categories (Model 2).</p>c<p>Additionally adjusted for personal history of BBD and family history of breast cancer (model used for homogeneity test) (Model 4).</p