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Distribution of MC 1 R variants among melanoma subtypes: p. R 163 Q is associated with lentigo maligna melanoma in a M editerranean population
Author(s) -
PuigButillé J.A.,
Carrera C.,
Kumar R.,
GarciaCasado Z.,
Badenas C.,
Aguilera P.,
Malvehy J.,
Nagore E.,
Puig S.
Publication year - 2013
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12418
Subject(s) - melanoma , odds ratio , nonsynonymous substitution , eye color , lentigo maligna , phototype , medicine , confidence interval , dermatology , biology , genetics , gene , genome
Summary Background Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC 1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC 1R variants and the risk of developing a specific subtype of melanoma has not been previously explored. Objectives To analyse whether certain MC 1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features. Methods An association study was performed between MC 1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients. Results We detected 53 MC 1 R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p. V 60L (30·0%), p. V 92 M (11·7%), p. D 294 H (9·4%), p. R 151 C (8·8%), p. R 160 W (6·2%), p. R 163 Q (4·2%) p. R 142 H (3·3%), p.I155 T (3·8%), p. V 122 M (1·5%) and p. D 84 E (1·0%). Melanoma subtypes showed differences in the total number of MC 1 R variants ( P = 0·028) and the number of red hair colour variants ( P = 0·035). Furthermore, an association between p. R 163 Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07–4·37; P = 0·044). No association was found between p. R 163 Q and F itzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC 1 R in pigmentation. No association was observed between MC 1 R polymorphisms and other melanoma subtypes. Conclusions Our findings suggest that certain MC 1 R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes.