title: Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin.
abstract: BACKGROUND
  Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin.
  
  
  METHODS
  Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions.
  
  
  RESULTS
  When samples were stratified by sex, we observed more SNPs associated with dark pigmentation and good sun tolerance in females than in males (107 versus 75; P = 2.32 × 10(-6)), who were instead associated with light pigmentation and poor sun tolerance. Furthermore, six SNPs in TYR, SILV/CDK2, GPR143, and F2RL1 showed strong differences in melanoma risk by sex (P < 0.01).
  
  
  CONCLUSIONS
  We demonstrate that these genetic variants are important for pigmentation as well as for melanoma risk, and also provide suggestive evidence for potential differences in genetic effects by sex.
authors.affiliation: Department of Medicine, Jaume I University of Castellon, Av. Sos Baynat s/n, 12071 Castellon, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hernando
authors.affiliation: Department of Medical Oncology, Biomedical Research Institute - INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010 Valencia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.affiliation: Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Lara P
authors.initials: LP
authors.lastname: Fernandez
authors.affiliation: Department of Medical Oncology, Biomedical Research Institute - INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010 Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.affiliation: Department of Medical Oncology, Biomedical Research Institute - INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010 Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Llorca-Cardeñosa
authors.affiliation: Department of Medical Oncology, Biomedical Research Institute - INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010 Valencia, Spain.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Oltra
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Bizkaia Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa, Bizkaia Spain.|BioCruces Health Research Institute, Cruces University Hospital, Cruces-Barakaldo, Bizkaia Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Boyano
authors.affiliation: Department of Medicine, Jaume I University of Castellon, Av. Sos Baynat s/n, 12071 Castellon, Spain.
authors.forename: Conrado
authors.identifier: 0000-0002-5252-563X
authors.initials: C
authors.lastname: Martinez-Cadenas
authors.affiliation: Department of Medical Oncology, Biomedical Research Institute - INCLIVA, University of Valencia, Av. Menendez Pelayo 4 accesorio, 46010 Valencia, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
keywords: Pigmentation; Polymorphisms; Sex; Skin cancer; UV sensitivity