title: Prospective association between dietary folate intake and skin cancer risk: results from the Supplémentation en Vitamines et Minéraux Antioxydants cohort.
abstract: BACKGROUND
  The role of folate in skin carcinogenesis is unclear, with experimental data suggesting potentially protective but also deleterious effects.
  
  
  OBJECTIVE
  Our main objective was to investigate the prospective association between dietary folate intake and risks of skin cancer (overall), nonmelanoma skin cancer (NMSC), and basal cell carcinoma (BCC). As an exploratory analysis, we also investigated the prospective association between erythrocyte folate concentration and skin cancer risk.
  
  
  METHODS
  In this study, we included 5880 participants in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort (follow-up: 1994-2007) who completed at least six 24-h dietary records during the first 2 y of the study. Associations between sex-specific tertiles of dietary and erythrocyte folate and skin cancer risk were assessed by using multivariate Cox proportional hazards models.
  
  
  RESULTS
  After a median follow-up of 12.6 y, 144 incident skin cancers were diagnosed. Dietary folate intake was associated with increased risk of overall skin cancer [HR for tertile 3 compared with tertile 1 (HR(T3vs.T1)): 1.79; 95% CI: 1.07, 2.99; P-trend = 0.03], NMSC (HR(T3vs.T1): 1.85; 95% CI: 1.06, 3.23; P-trend = 0.03), and BCC (HR(T3vs.T1): 1.78; 0.98, 3.24; P-trend = 0.05). This association was observed in women (corresponding P-trend = 0.007, 0.009, and 0.009, respectively) but not in men (P-trend = 0.8, 0.8, and 0.9, respectively). P-interaction values between tertiles of dietary folate intake and sex were 0.04, 0.02, and 0.02 for overall skin cancer, NMSC, and BCC, respectively. Erythrocyte folate concentration was directly associated with increased risk of overall skin cancer (HR(T3vs.T1): 2.54; 95% CI: 0.95, 6.81; P-trend = 0.03), NMSC (HR(T3vs.T1): 3.49; 95% CI: 1.11, 11.0; P-trend = 0.01), and BCC (HR(T3vs.T1): 7.44; 95% CI: 1.57, 35.3; P-trend = 0.004) (men and women combined).
  
  
  CONCLUSIONS
  This prospective study suggests an association between dietary folate intake and erythrocyte folate concentration and increased risk of overall skin cancer, NMSC, and BCC. Although several mechanistic hypotheses and 2 previous large prospective studies on BCC are in line with these results, epidemiologic literature is limited, and future research is needed to better elucidate the potential role of folate in the cause of skin cancers.
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Donnenfeld
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France;
authors.forename: Mélanie
authors.initials: M
authors.lastname: Deschasaux
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France;
authors.forename: Paule
authors.initials: P
authors.lastname: Latino-Martel
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France;
authors.forename: Abou
authors.initials: A
authors.lastname: Diallo
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France;
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France; Public Health Department, Avicenne Hospital, Bobigny, France; and.
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France; Dermatology Department, Saint André Hospital, Bordeaux, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, French National Institute of Health and Medical Research U1153, French National Institute for Agricultural Research U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team, Bobigny, France; m.touvier@eren.smbh.univ-paris13.fr.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Touvier
mesh_terms: D000328:Adult; D002280:Basal Cell Carcinoma / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D015331:Cohort Studies; D004032:Diet / Q000009:adverse effects*; D015930:Diet Records; D004311:Double-Blind Method; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000009:adverse effects* / Q000097:blood; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D059012:Lost to Follow-Up; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D012737:Sex Factors; D012878:Skin Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*
chemical_list: D005492:Folic Acid
keywords: BCC; NMSC; folate; prospective study; skin cancer risk