title: MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project.
abstract: BACKGROUND
  The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.
  
  
  METHODS
  Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.
  
  
  RESULTS
  Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.
  
  
  CONCLUSIONS
  Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tagliabue
authors.affiliation: Department of Dermatology, University of L'Aquila, 47100 L'Aquila, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Fargnoli
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gandini
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Maisonneuve
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Kayser
authors.affiliation: Department of Dermatology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Nijsten
authors.affiliation: 1] Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [2] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [3] Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Dermatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: N A
authors.initials: NA
authors.lastname: Gruis
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale Cancer Center, New Haven, CT 06520-8034, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Institute of Forensic Research, 31-033 Krakow, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Branicki
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Victoria 3052, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Dwyer
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, 7001 Australia.
authors.forename: L
authors.initials: L
authors.lastname: Blizzard
authors.affiliation: Department of Pathology, Oslo University Hospital, N-0027 Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Helsing
authors.affiliation: International Prevention Research Institute, Lyon 69006, France.
authors.forename: P
authors.initials: P
authors.lastname: Autier
authors.affiliation: Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, 30100 Murcia, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: García-Borrón
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Kanetsky
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Landi
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada ON K1N 6N5.
authors.forename: J
authors.initials: J
authors.lastname: Little
authors.affiliation: Section of Epidemiology and Biostatistics, Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
authors.forename: J
authors.initials: J
authors.lastname: Newton-Bishop
authors.affiliation: UCL Institute of Child Health, London WC1N 1EH, UK.
authors.forename: F
authors.initials: F
authors.lastname: Sera
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Raimondi
mesh_terms: D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006200:Hair Color; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012306:Risk; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*
chemical_list: D044102:Receptor, Melanocortin, Type 1