Document Detail


Polymorphisms in the p27kip-1 and prohibitin genes denote novel genes associated with melanoma risk in Brazil, a high ultraviolet index region.
MedLine Citation:
PMID:  23624368     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Guilherme Francisco; Fernanda T Gonçalves; Olinda C Luiz; Renata F Saito; Rodrigo A Toledo; Tomoko Sekiya; Tharcísio C Tortelli; Esther D V B Violla; Tatiane K Furuya Mazzotti; Priscila D R Cirilo; Cyro Festa-Neto; José A Sanches; Gilka J F Gattás; José Eluf-Neto; Roger Chammas
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  Melanoma research     Volume:  23     ISSN:  1473-5636     ISO Abbreviation:  Melanoma Res.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-4-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  231-236     Citation Subset:  -    
Affiliation:
aExperimental Oncology Laboratory, Medical Investigation Laboratory, Unit 24, Department of Radiology bMedical Investigation Laboratory, Unit 40, Department of Legal Medicine, Medical Ethics, Social and Occupational Medicine cMedical Investigation Laboratory, Unit 38, Department of Preventive Medicine dEndocrine Genetics Unit, Medical Investigation Laboratory, Unit 25, Department of Internal Medicine, Endocrinology eDepartment of Dermatology fCenter for Translational Oncology, São Paulo State Cancer Institute (ICESP), School of Medicine, University of São Paulo, São Paulo, Brazil.
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