Journal Article

Genetic Polymorphisms in the Base Excision Repair Pathway and Cancer Risk: A HuGE Review

Rayjean J. Hung, Janet Hall, Paul Brennan and Paolo Boffetta

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 162, issue 10, pages 925-942
Published in print November 2005 | ISSN: 0002-9262
Published online October 2005 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwi318
Genetic Polymorphisms in the Base Excision Repair Pathway and Cancer Risk: A HuGE Review

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Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to cancer risk. However, epidemiologic findings have been inconsistent. The authors conducted meta-analyses of associations between genes in the base excision repair pathway and cancer risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1). They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity. They found a protective effect of the XRCC1 194Trp allele for tobacco-related cancers (OR = 0.86, 95% CI: 0.77, 0.95), using 4,895 cases and 5,977 controls from 16 studies; this is compatible with evidence of lower mutagen sensitivity for this allele. The XRCC1 399Gln/399Gln genotype was associated with increased risk of tobacco-related cancers among light smokers (OR = 1.38, 95% CI: 0.99, 1.94) but decreased risk among heavy smokers (OR = 0.71, 95% CI: 0.51, 0.99), suggesting effect modification by tobacco smoking. There was no association between cancer risk and the APE1/APEX1 Asp148Glu and XRCC1 Arg280His polymorphisms. Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure.

Keywords: apurinic/apyrimidinic endonuclease; DNA repair; meta-analysis; neoplasms; 8-oxoguanine DNA glycosylase, human; polymorphism, genetic; XRCC1 protein; APE1/APEX1, apurinic/apyrimidinic endonuclease; CI, confidence interval; dbSNP, Database of Single Nucleotide Polymorphisms; OGG1, 8-oxoguanine DNA glycosylase; OR, odds ratio; XRCC1, x-ray repair cross-complementing group 1

Journal Article.  8306 words.  Illustrated.

Subjects: Public Health and Epidemiology

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