Carcinogenesis Advance Access published online on October 24, 2007
Carcinogenesis, doi:10.1093/carcin/bgm211
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Genetic Polymorphisms in the Apoptosis-Associated Genes FAS and FASL and Breast Cancer Risk
Department of Medicine and the Herbert Irving Comprehensive Cancer Center, Columbia University, 161 Fort Washington Avenue, 10-1072, New York, NY 10032, USA,
1 Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599-7435, USA,
2 Department of Epidemiology, Columbia University, NY 10032, USA,
3 Department of Epidemiology, University of North Texas Health Science Center at Fort Worth, NY 10032, USA,
4 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, NY, USA,
5 Global Epidemiology, Pfizer, NY, USA and
6 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, NY, USA
* kd59{at}columbia.edu
FAS and FASL play key roles in apoptotic signaling and down-regulation of this pathway may facilitate tumorigenesis. Alterations in apoptosis genes may affect cancer risk by influencing individual susceptibility to environmental carcinogens. Using a population-based breast cancer case-control study on Long Island, New York, we examined whether polymorphisms in FAS and FASL modified the association between breast cancer risk and a marker of environmental exposures, polycyclic aromatic hydrocarbon (PAH)-DNA adducts. We examined polymorphisms in FAS (5'UTR -1377G/A and 5'UTR -670G/A) and FASL (5'UTR -844C/T) in 1,053 breast cancer cases and 1,102 population-based controls. There was no significant association between these genetic polymorphisms and breast cancer risk. The presence of at least one variant allele (GA or AA) in FAS1377 was associated with a 36% increase in breast cancer risk among those with detectable PAH-DNA adduct levels (OR = 1.36, 95% CI = 1.01-1.83). In addition, lactation history significantly modified the association between FAS1377 and FAS670 genetic variants and breast cancer risk (OR = 1.46, 95% CI = 1.04-2.06 and OR = 1.71, 95% CI = 1.13-1.58, respectively in those who ever lactated compared to those who did not with the wild-type alleles). Overall, this study suggests that the risk of breast cancer may be elevated among women with polymorphisms in the FAS gene and detectable PAH-DNA adducts.
Received June 26, 2007; revised August 16, 2007; accepted September 12, 2007.
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