Journal Article

<i>ERCC2</i> /<i>XPD</i> Gene Polymorphisms and Lung Cancer: A HuGE Review

Simone Benhamou and Alain Sarasin

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 161, issue 1, pages 1-14
Published in print January 2005 | ISSN: 0002-9262
Published online January 2005 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwi018
ERCC2 /XPD Gene Polymorphisms and Lung Cancer: A HuGE Review

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The xeroderma pigmentosum group D (XPD) protein is a well-characterized DNA helicase necessary for the nucleotide excision repair of bulky DNA lesions, such as those induced by cigarette smoking. Polymorphisms in several exons of the XPD gene have been identified; two of them, Asp312Asn and Lys751Gln, are common and result in an amino acid change. Most of the reported data indicate higher levels of DNA adducts in people carrying variant Asn or Gln alleles, which suggests that these persons have lower repair efficiency. These two polymorphisms have been hypothesized to modify the risk of lung cancer. To examine this association, the authors undertook a review and meta-analyses of nine published case-control studies. No clear association between XPD Asp312Asn or XPD Lys751Gln gene polymorphisms and lung cancer was found. However, it may be only the joint effect of multiple polymorphisms within the gene that provides information about an association with lung cancer. Because of advances in high-throughput genotyping techniques, it is likely that future association studies on lung cancer will need to investigate multiple polymorphisms within genes and multiple genes within the same pathway and will need to use recently developed haplotype-based methods to evaluate the haplotypic effects.

Keywords: epidemiology; ERCC-2 protein; ERCC2/XPD; genetics; lung neoplasms; polymorphism (genetics); xeroderma pigmentosum; ASR, world age-standardized rate per 100,000; CI, confidence interval; CYP, cytochrome P-450; EPHX, epoxide hydrolase; ERCC2, excision repair cross-complementing rodent repair deficiency, group 2; GST, glutathione S-transferase; MPO, myeloperoxidase; XPD, xeroderma pigmentosum group D; XRCC1, x-ray cross-complementing group 1.

Journal Article.  8621 words.  Illustrated.

Subjects: Public Health and Epidemiology

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