title: Polymorphisms in the p27kip-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.
authors.affiliation: Experimental Oncology Laboratory, Medical Investigation Laboratory, Unit 24, Department of Radiology.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Francisco
authors.forename: Fernanda T
authors.initials: FT
authors.lastname: Gonçalves
authors.forename: Olinda C
authors.initials: OC
authors.lastname: Luiz
authors.forename: Renata F
authors.initials: RF
authors.lastname: Saito
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Toledo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sekiya
authors.forename: Tharcísio C
authors.initials: TC
authors.lastname: Tortelli
authors.forename: Esther D V B
authors.initials: ED
authors.lastname: Violla
authors.forename: Tatiane K
authors.initials: TK
authors.lastname: Furuya Mazzotti
authors.forename: Priscila D R
authors.initials: PD
authors.lastname: Cirilo
authors.forename: Cyro
authors.initials: C
authors.lastname: Festa-Neto
authors.forename: José A
authors.initials: JA
authors.lastname: Sanches
authors.forename: Gilka J F
authors.initials: GJ
authors.lastname: Gattás
authors.forename: José
authors.initials: J
authors.lastname: Eluf-Neto
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
mesh_terms: D001938:Brazil; D016022:Case-Control Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays
chemical_list: C436291:CDKN1B protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27