Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants

作者：Ozola Aija^*; Azarjana Kristine; Donina Simona; Proboka Guna; Mandrika Ilona; Petrovska Ramona; Cema Ingrida; Heisele Olita; Engele Ludmila; Streinerte Baiba; Pjanova Dace

来源：Cancer Genetics, 2013, 206(3): 81-91.

DOI：10.1016/j.cancergen.2013.01.002

• Melanocortin 1 receptor gene
• melanoma
• rare MC1R variants
• pigmentation
• functionality of MC1R variants

To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165lle and Val188lle, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (Cl) 2.19-9.14, P < 0.001). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% Cl 2.15-7.38, P < 0.001) that of carriers of one variant (OR 1.98, 95% Cl 1.26-3.11, P = 0.003). After stratification according to the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.

• 出版日期2013-3