American Journal of Epidemiology Advance Access originally published online on May 17, 2006
American Journal of Epidemiology 2006 164(4):297-302; doi:10.1093/aje/kwj189
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Human Genome Epidemiology (HuGE) Review |
XRCC3 and XPD/ERCC2 Single Nucleotide Polymorphisms and the Risk of Cancer: A HuGE Review
1 Section of Epidemiology, ISI Foundation (Institute for Scientific Interchange), Torino, Italy
2 Section of Biostatistics and Epidemiology, Dartmouth Medical School, Lebanon, NH
3 Division of Epidemiology and Biostatistics, Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM
4 Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom
5 Department of Genetics, Biology and Biochemistry, Faculty of Medicine and Surgery, University of Torino, Torino, Italy
Correspondence to Dr. Giuseppe Matullo, Section of Epidemiology, ISI Foundation, Viale Settimio Severo 65, 10133 Torino, Italy (e-mail: matullo{at}isiosf.isi.it).
Hundreds of polymorphisms in DNA repair genes have been identified; however, for many of these polymorphisms, the impact on repair phenotype and cancer susceptibility remains uncertain. In this review, the authors focused on the x-ray repair cross-complementing protein group 3 (XRCC3) and xeroderma pigmentosum group D (XPD)/excision repair cross-complementing rodent repair deficiency (ERCC2) genes, because they are among the most extensively studied but no final conclusion has yet been drawn about their role in cancer occurrence. XRCC3 participates in DNA double-strand break/recombinational repair through homologous recombination to maintain chromosome stability. XPD/ERCC2 is a helicase involved in the nucleotide excision repair pathway, which recognizes and repairs many structurally unrelated lesions, such as bulky adducts and thymidine dimers. The authors identified a sufficient number of epidemiologic studies on cancer to perform meta-analyses for XPD/ERCC2 variants in codons 156, 312, and 751 and XRCC3 variants in codon 241. The authors evaluated all cancer sites to investigate whether DNA repair is likely to take place in a rather nonspecific manner for different carcinogens and different cancers. For the most part, the authors found no association between these genes and the cancer sites investigated, except for some statistically significant associations between XPD/ERCC2 single nucleotide polymorphisms and skin, breast, and lung cancers.
ERCC2; ERCC2 protein, human; genetics; meta-analysis; neoplasms; XPD; XRCC3; x-ray repair cross complementing protein 3
Abbreviations: ERCC, excision repair cross-complementing rodent repair deficiency; HuGE, Human Genome Epidemiology; SNP, single nucleotide polymorphism; XPD, xeroderma pigmentosum group D; XRCC, x-ray repair cross-complementing protein
Editor's note: This article is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).
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