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Carcinogenesis Advance Access originally published online on August 25, 2009
Carcinogenesis 2009 30(10):1735-1743; doi:10.1093/carcin/bgp207
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis

Simone Mocellin*, Daunia Verdi and Donato Nitti

Department of Oncological and Surgical Sciences, Meta-analysis Unit, University of Padova, via Giustiniani 2, 35128 Padova, Italy

* To whom correspondence should be addressed. Clinica Chirurgica Generale 2, Dipartimento di Scienze Oncologiche e Chirurgiche, Università di Padova, via Giustiniani 2, 35128 Padova, Italy. Tel: +39 049 8211851; Fax: +39 049 651891; Email: mocellins{at}hotmail.com

Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03–1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

Abbreviations: CI, confidence interval; HWE, Hardy–Weinberg equilibrium; NER, nucleotide excision repair; OR, odds ratio; RFLP, restriction fragment length polymorphism; SNP, single-nucleotide polymorphism

Received June 19, 2009; revised August 14, 2009; accepted August 15, 2009.


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