Polymorphisms in the p27 kip-1 and prohibitin genes denote novel genes associated with melanoma risk in Brazil, a high ultraviolet index region

Abstract

Ultraviolet (UV) radiation is a major environmental risk factor to the development of cutaneous melanoma as it induces pyrimidine dimers in DNA. Genes that exert their function by arresting the cell cycle are critical to avoid carcinogenic mutations, allowing the processing of DNA repair systems. This study was carried out to evaluate the role of polymorphisms in cell cycle genes such as TP53, p27, CDKN2A, prohibitin, and GADD153 in melanoma risk as well as their influence on known risk factors in a high UV index region. A hospital-based case-control study was carried out in Brazil to evaluate the contribution of polymorphisms in cell cycle genes toward melanoma risk. The study comprised 202 melanoma patients and 210 controls. The polymorphisms analyzed were TP53 Arg72Pro, p27 Val109Gly, GADD153 Phe10Phe (rs697221), CDKN2A 3'UTR C540G, and prohibitin 3'UTR C1703T. As regards, p27 Val109Gly, both heterozygous and homozygous Gly genotypes were shown to be protective genotypes on calculating both crude and adjusted odds ratios (ORs) for age, sex, and educational level [OR 0.37; 95% confidence interval (CI) 0.16-0.87; P<0.05]. Similarly, the prohibitin TT genotype increased melanoma risk in the crude and adjusted analyses (OR 2.40; 95% CI 1.10-5.26; P<0.05). The p27 Gly protective genotype decreased the risk for melanoma in a stratified analysis of the known risk factors such as hair and eye color, sunburns, pigmented lesions, and European ancestry. The prohibitin TT genotype increased the risk of melanoma by such host factors. Our results showed for the first time that polymorphisms in p27 Val109Gly and in prohibitin 3'UTR C1703T genotypes modulate the risk to melanoma in a high UV index region.