XPD Polymorphism and Risk of Subsequent Cancer in Individuals with Nonmelanoma Skin Cancer
- Abenaa M. Brewster1,
- Anthony J. Alberg2,
- Paul T. Strickland3,
- Sandy C. Hoffman2 and
- Kathy Helzlsouer2
- 1Department of Clinical Cancer Prevention, University of Texas M.D. Anderson Cancer Center, Houston, Texas and Departments of 2Epidemiology and 3Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
- Requests for reprints:
Kathy Helzlsouer, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Suite E6132, 615 North Wolfe Street, Baltimore, MD 21205. Phone: 410-955-9727; Fax: 410-614-2632. E-mail: khelzlso{at}jhsph.edu
Abstract
Background: Individuals with nonmelanoma skin cancer (NMSC) are at increased risk of developing subsequent cancers. Genetic predisposition to reduced DNA repair capacity may be an underlying susceptibility factor explaining the excess risk of malignancies. To test this hypothesis, a cohort study was conducted to examine the association between XPD Lys751Gln polymorphism and risk of a second primary cancer in individuals with NMSC. Methods: A subgroup of 481 individuals with a history of NMSC who participated in the CLUE II community-based cohort was followed for the development of a second primary cancer. Blood specimens donated in 1989 were genotyped for the XPD Lys751Gln polymorphism using the 5′ nuclease assay. Cox proportional regression with delayed entry was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (95% CI) for risk of developing a second primary cancer according to XPD genotype. All statistical tests were two sided. Results: Eighty individuals developed a second primary cancer. The most frequent occurring cancers were of the prostate (18%), lung (15%), and breast (15%). Persons with at least one Gln allele had an increased risk of a second primary cancer compared with the reference Lys/Lys genotype (adjusted IRR 2.22, 95% CI 1.30-3.76). When the reference category was limited to never smokers with the Lys/Lys genotype, the risk of developing a second primary cancer associated with having at least one Gln allele was increased >3-fold in both never smokers (IRR 3.93, 95% CI 1.36-11.36) and ever smokers (IRR 6.14, 95% CI 2.17-17.37). Conclusion: These findings suggest that individuals with NMSC who have the variant XPD Gln allele are at increased risk of developing a second primary cancer.
Footnotes
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Grant support: National Institute of Aging grant 5U01AG018033, National Cancer Institute grant 5U01CA086308, and National Institute of Environmental Health Sciences grant P30 ES03819. Minority Supplement of Clinical Oncology Research Career Development Program (K12-CA01709) from the National Cancer Institute (A.M. Brewster) and KO7 award (CA73790) from the National Cancer Institute (A.J. Alberg).
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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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- Accepted March 11, 2004.
- Received December 29, 2003.
- Revision received March 3, 2004.
