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JNCI Journal of the National Cancer Institute 2002 94(2):94-101; doi:10.1093/jnci/94.2.94
© 2002 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 94, No. 2, 94-101, January 16, 2002
© 2002 Oxford University Press


ARTICLE

DNA Repair, Dysplastic Nevi, and Sunlight Sensitivity in the Development of Cutaneous Malignant Melanoma

Maria Teresa Landi, Andrea Baccarelli, Robert E. Tarone, Angela Pesatori, Margaret A. Tucker, Mohammad Hedayati, Lawrence Grossman

Affiliations of authors: M. T. Landi, M. A. Tucker (Genetic Epidemiology Branch), R. E. Tarone (Biostatistics Branch), Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; A. Baccarelli, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and Epidemiology Research Center, University of Milan, Italy; A. Pesatori, Epidemiology Research Center, University of Milan; M. Hedayati, L. Grossman, Department of Biochemistry, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD.

Correspondence to: Maria Teresa Landi, M.D., Ph.D., National Institutes of Health, 6120 Executive Blvd., EPS 7114, Bethesda, MD 20892–7236 (e-mail: landim{at}mail.nih.gov).

Background: Exposure to UV radiation is associated with cutaneous malignant melanoma (CMM). In mammalian cells, UV radiation induces DNA damage that can be repaired by the nucleotide excision repair system. We designed this case–control study to determine whether DNA repair capacity (DRC) is associated with the risk of CMM and to identify risk factors that may interact biologically with DRC in the development of melanoma. Methods: Global DRC was measured in lymphocytes with the host-cell reactivation assay. Data were analyzed by use of multiple regression models. All statistical tests were two-sided. Results: DRC could be determined for 132 case patients with incident melanoma and for 145 age- and sex-matched control subjects. No statistically significant association between melanoma risk and DRC by itself was found (odds ratio [OR] = 1.0; 95% confidence interval [CI] = 0.6 to 1.7, adjusted for age, sex, lymphocyte viability, and sample storage time). DRC, however, strongly influenced CMM risk in individuals with a low tanning ability or dysplastic nevi. Individuals with a low tanning ability and a low DRC had a higher risk for CMM (OR = 8.6; 95% CI = 2.7 to 27.5) than individuals with a higher tanning ability and a high DRC. Likewise, individuals with dysplastic nevi and a low DRC had a higher relative risk (OR = 6.7; 95% CI = 2.4 to 18.6) than those lacking dysplastic nevi and having a high DRC. Subjects with dysplastic nevi and a high DRC had an intermediate risk. A likelihood-ratio test gave statistically significant interactions between DRC and tanning response (P = .001) and between DRC and dysplastic nevus status (P = .04), which were independently associated with CMM risk. Conclusions: DRC may modify the risk for melanoma in the presence of other strong risk factors, such as a low tanning ability and the presence of dysplastic nevi. The occurrence of melanoma in subjects without these risk factors appears to be independent of DRC.



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