Variants of the MATP/SLC45A2 gene are protective for melanoma in the French population.
In this study, we investigated whether variants in three key pigmentation genes-MC1R, MATP/SLC45A2, and OCA2--were involved in melanoma predisposition. A cohort comprising 1,019 melanoma patients (MelanCohort) and 1,466 Caucasian controls without skin cancers were studied. A total of 10 polymorphisms, including five functional MC1R alleles (p.Asp84Glu, p.Arg142His, p.Arg151Cys, p.Arg160Trp, and p.Asp294His), two nonsynonymous SLC45A2 variants (p.Phe374Leu and p.Glu272Lys), and three intronic OCA2 variants previously shown to be strongly associated with eye color (rs7495174 T>C, rs4778241 G>T, and rs4778138 T>C) were genotyped. As expected, MC1R variants were closely associated with melanoma risk (P value <2.20.10(-16); odds ratio [OR]=2.29 [95% confidence interval, CI=1.85-2.82 and OR=3.3 [95% CI=2.00-5.45], for the presence of one or two variants, respectively). Interestingly, the SLC45A2 variant p.Phe374Leu was significantly and strongly protective for melanoma (P-value=2.12.10(-15); OR=0.35 [95% CI=0.26-0.46] and OR=0.32 [95% CI=0.24-0.43], considering the genotypes Phe/Leu and Leu/Leu, respectively). MC1R and SLC45A2 variants had additive effects on melanoma risk, and after adjusting for pigmentation characteristics, the risk was persistent, even though both genes had a strong impact on pigmentation. Future studies may show whether genetic information could provide a useful complement to physical examination in predicting melanoma risk.
Guedj
Mickaël
M
Laboratoire Statistique et Génome, UMR CNRS 8071, INRA 1152, Université d'Evry Val d'Essonne, Evry, France.
Bourillon
Agnès
A
Combadières
Christophe
C
Rodero
Mathieu
M
Dieudé
Philippe
P
Descamps
Vincent
V
Dupin
Nicolas
N
Wolkenstein
Pierre
P
Aegerter
Philippe
P
Lebbe
Céleste
C
Basset-Seguin
Nicole
N
Prum
Bernard
B
Saiag
Philippe
P
Grandchamp
Bernard
B
Soufir
Nadem
N
D000951:Antigens, Neoplasm / Q000235:genetics*; D016022:Case-Control Studies; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics
D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; D044102:Receptor, Melanocortin, Type 1; C510061:SLC45A2 protein, human