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Carcinogenesis Advance Access published online on March 20, 2007
Carcinogenesis, doi:10.1093/carcin/bgm063
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Susceptibility to arsenic-induced skin lesions from polymorphisms in base excision repair genes

Carrie V. Breton1, Wei Zhou2, Molly L. Kile2, E. Andres Houseman3, Quazi Quamruzzaman4, Mahmuder Rahman4, Golam Mahiuddin4 and David C. Christiani1,2

1 Harvard School of Public Health, Dept of Epidemiology, 677 Huntington Avenue, Boston, MA 02115
2 Harvard School of Public Health, Dept of Environmental Health, 665 Huntington Avenue, Boston, MA 02115
3 University of Massachusetts Lowell, Department of Work Environment, Kitson Hall, 202E, One University Avenue Lowell, MA 01854
4 Dhaka Community Hospital, 190/1 Baro Moghbazar, Wireless Railgate, 1217, Dhaka, Bangladesh

All correspondence should be Sent To: Carrie Breton, Harvard School of Public Health, Department of Environmental Health, Building I, Room 1420, 665 Huntington Ave, Boston MA 02115, Phone: 617-416-9897; Fax: 617-432-3441, Email: cbreton{at}hsph.harvard.edu

Genetic polymorphisms in the base excision DNA repair pathway may influence individual susceptibility to arsenic and the development of arsenic-induced skin lesions. Data from a case-control study of 792 cases and 792 matched controls conducted in Bangladesh from 2001-2003 were analyzed using conditional logistic regression to assess the associations between four common base excision repair genetic polymorphisms XRCC1 Arg399Gln, XRCC1 Arg194Trp, hOGG1 Ser326Cys, and APE1 Asp148Glu and arsenic-induced skin lesions including melanosis and keratosis. Adjusted for toenail arsenic, BMI, education, smoking and betelnut use, individuals with the APE1 148Glu/Glu polymorphism had a two-fold increased odds of skin lesions compared to individuals with the 148Asp/Asp genotype (1.93; 95% CI 1.15, 3.19). Gene-environment interactions between toenail arsenic and XRCC1 Arg194Trp and APE1 Asp148Glu were observed. Within the lowest arsenic tertile, APE1 148Glu/Glu had 2.5 times the odds ratio compared to wildtype, whereas within the highest tertile of arsenic the odds ratios for skin lesions did not differ. In contrast, at low arsenic levels the odds ratios for skin lesions did not differ much by XRCC1 Arg194Trp genotype. However, at the highest tertile of arsenic the XRCC1 194Arg/Arg polymorphism conferred a three-fold larger odds ratio for skin lesions compared to XRCC1 194Trp/Trp. Individuals may have different odds for developing skin lesions based in part on their genetic profile for BER and their arsenic exposure history. Future research on arsenic-induced skin lesions should consider the impact of genetic variation to individual susceptibility to arsenic toxicity.

Received November 28, 2006; revised January 23, 2007; accepted March 15, 2007.


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