Polymorphisms in DNA Repair Genes and Associations with Cancer Risk1
- Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and Department of Epidemiology, University of Washington, Seattle, Washington 98195
Abstract
Common polymorphisms in DNA repair genes may alter protein function and an individual’s capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by NIH Grants CA59045 and T32-CA09661.
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↵2 To whom requests for reprints should be addressed, at Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, P. O. Box 19024, MP-900, Seattle, WA 98109-1024. Phone: (206) 667-7617; Fax: (206) 667-7850; E-mail: nulrich{at}fhcrc.org
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↵3 The abbreviations used are: BER, base-excision repair; APEX, apurinic/apyrimidinic endonuclease; XRCC1, X-ray repair complementing defective in Chinese hamster 1; NER, nucleotide-excision repair; XPC, xeroderma pigmentosum complementation group C; TFIIH, transcription factor IIH; XPD, xeroderma pigmentosum complementation group D; ERCC1, excision-repair cross-complementing 1; XPF, xeroderma pigmentosum complementation group F; XRCC3, X-ray repair complementing defective in Chinese hamster 3; LIG4, ligase IV; MMR, mismatch repair; SCCHN, squamous cell carcinoma of the head and neck; OR, odds ratio; CI, confidence interval; UTR, untranslated region; NAT-2, N-acetyltransferase type 2.
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↵4 National Center for Biotechnology Information. DbSNP: http://www.ncbi.nlm.nih.gov/SNP/.
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↵5 National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez.
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↵6 Mohrenweiser, H. W., Xi, T., Vazquez-Matas, J., and Jones, J. M. Identification of 127 Amino Acid Substitution Variants in Screening 37 DNA Repair Genes in Humans. Cancer Epidemiol. Biomark Prev. 11: 1054–1064, 2002.
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- Accepted September 26, 1902.
- Received May 31, 1902.
- Revision received September 20, 1902.
