title: MC1R, SLC45A2 and TYR genetic variants involved in melanoma susceptibility in southern European populations: results from a meta-analysis.
abstract: METHODS
  Seven genetic biomarkers previously associated with melanoma were analysed in a meta-analysis conducted in three South European populations: five red hair colour (RHC) MC1R alleles, one SLC45A2 variant (p.Phe374Leu) and one thermosensitive TYR variant (p.Arg402Gln). The study included 1639 melanoma patients and 1342 control subjects.
  
  
  RESULTS
  The estimated odds ratio (OR) associated with carrying at least one MC1R RHC variant was 2.18 (95% confidence interval (CI): 1.86-2.55; p-value=1.02×10(-21)), with an additive effect for carrying two RHC variants (OR: 5.02, 95% CI: 2.88-8.94, p-value=3.91×10(-8)). The SLC45A2 variant, p.Phe374Leu, was significantly and strongly protective for melanoma in the three South European populations studied, with an overall OR value of 0.41 (95% CI: 0.33-0.50; p-value=3.50×10(-17)). The association with melanoma of the TYR variant p.Arg402Gln was also statistically significant (OR: 1.50; 95% CI: 1.11-2.04; p-value=0.0089). Adjustment for all clinical potential confounders showed that melanoma risks attributable to MC1R and SLC45A2 variants strongly persisted (OR: 2.01 95% CI: 1.49-2.72 and OR: 0.50, 95% CI: 0.31-0.80, respectively), while the association of TYR p.Arg402Gln was no longer significant. In addition, stratification of clinical melanoma risk factors showed that the risk of melanoma was strong in those individuals who did not have clinical risk factors.
  
  
  CONCLUSIONS
  In conclusion, our results show without ambiguity that in South European populations, MC1R RHC and SCL45A2 p.Phe374Leu variants are strong melanoma risk predictors, notably in those individuals who would not be identified as high risk based on their phenotypes or exposures alone. The use of these biomarkers in clinical practice could be promising and warrants further discussion.
authors.affiliation: Department of Haematology and Medical Oncology, Fundacion Investigacion Hospital Clinico-INCLIVA, Valencia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.forename: Hui-Han
authors.initials: HH
authors.lastname: Hu
authors.forename: Mickaël
authors.initials: M
authors.lastname: Guedj
authors.forename: Lara P
authors.initials: LP
authors.lastname: Fernandez
authors.forename: Vincent
authors.initials: V
authors.lastname: Descamps
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Armand
authors.initials: A
authors.lastname: Benssussan
authors.forename: Philippe
authors.initials: P
authors.lastname: Saiag
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Fargnoli
authors.forename: Ketty
authors.initials: K
authors.lastname: Peris
authors.forename: Jose A
authors.initials: JA
authors.lastname: Aviles
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006200:Hair Color / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008545:Melanoma / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000235:genetics*; D014442:Monophenol Monooxygenase / Q000235:genetics*; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D012880:Skin Pigmentation / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; D044102:Receptor, Melanocortin, Type 1; C510061:SLC45A2 protein, human; D014442:Monophenol Monooxygenase