Genetic Variants of Melanocortin 1 Receptor (MC1R) Gene and Skin Cancer Risk Prediction

The melanocortin-1 receptor (MC1R) gene (Mendelian Inheritance in Man 155555), plays an important role in the pigmentation process. The MC1R gene is low penetrating and highly polymorphic. A number of literature has studied the association of MC1R variants with skin cancer risk. Here, our objective is to shortlist the most potential MC1R variants based on sequence to structure and structure to function relationship. Out of total 1238 reported SNPs in MC1R, 258 were missense variants, of which, 11 were reported to be associated with cancer risk, according to earlier reports. Missense substitutions are of immense significance, as it causes the alterations in amino acid. Through in silico study, we have narrowed down three most potential variants i. e. R151C, R160W and D294H based on their functional prediction. Our next target was to identify other significant variations, if any, from remaining 247 SNPs, which are not reported earlier. We used several web based tools including SIFT, Mutation Taster, Polyphene2 and Meta-SNP and predicted six novel SNPs that might have crucial role in skin cancer. It is interesting to mention here that a number of literature identified the association of D84E (Aspartic acid to Glumatic acid at codon 84) and V60L (Valine to Leucine at codon 60) with skin cancer risk, although their similarity does not explain the association. We have attempted to explain the above ambiguity with secondary RNA structure of these two substitutions. To the best of our knowledge this is the first attempt to correlate the SNPs with structural prediction.