title: Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Cancer Control Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Kvaskoff
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bijon
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mesrine
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Vilier
authors.affiliation: Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Victoria, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, University of Melbourne, Victoria, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fournier
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.affiliation: "Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology*; D005190:Family; D005260:Female; D005602:France; D006801:Humans; D016015:Logistic Models; D008544:Melanocytes; D008875:Middle Aged; D009506:Nevus / Q000150:complications*; D017697:Premenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000150:complications*