MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project

PASQUALI E; GARCÍA-BORRÓN JC; FARGNOLI MC; GANDINI S; MAISONNEUVE P; BAGNARDI V; SPECCHIA C; LIU F; KAYSER M; NIJSTEN T; NAGORE E; KUMAR R; HANSSON J; KANETSKY PA; GHIORZO P; DEBNIAK T; BRANICKI W; GRUIS NA; HAN J; DWYER T; BLIZZARD L; LANDI MT; PALMIERI G; RIBAS G; STRATIGOS A; COUNCIL ML; AUTIER P; LITTLE J; NEWTON-BISHOP J; SERA F; RAIMONDI S; LITTLE J; CAINI S; HOFMAN A; KAYSER M; UITTERLINDEN AG; SCHERER D; HOIOM V; PASTORINO L; COCHRANE J; FERNANDEZ-DE-MISA R; MORLING N; JOHANSEN P; PFEIFFER R; KYPREOU K; BOWCOCK A; CORNELIUS L; COUNCIL ML; MOTOKAWA T; ANNO S; HELSING P; ANDRESEN PA; WONG TH; BERWICK M; BEGG C; ORLOW I; MUJUMDAR U; HUMMER A; BUSAM K; ROY P; CANCHOLA R; CLAS B; COTIGNOLA J; MONROE Y; ARMSTRONG B; KRICKER A; LITCHFIELD M; DWYER T; TUCKER P; STEPHENS N; GALLAGHER R; SWITZER T; MARRETT L; THEIS B; FROM L; CHOWDHURY N; VANASSE L; PURDUE M; NORTHRUP D; ZANETTI R; ROSSO S; ANTON-CULVER H; LEIGHTON N; GILDEA M; GRUBER S; BONNER J; JETER J; KLOTZ J; WILCOX H; WEISS H; MILLIKAN R; THOMAS N; MATTI

INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.

JOHN WILEY & SONS INC

Lugar: New York; Año: 2015 vol. 136 p. 618 - 631

0020-7136

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects.