Abstract
Abstract Breast cancer risk has been associated with tobacco smoking or deficient DNA repair. However, limited previous studies have focused on genetic susceptibility-exposure interactions. Using T-lymphocytes collected in a breast cancer case-control study (357 controls and 360 cases), this study tested whether the association between smoking and breast cancer risk is modified by individual's nucleotide excision repair capacity (NERC) using a newly developed plasmid-based electroporation assay. There was a significant age-dependent decline of NERC in controls (p=0.01) but not in breast cancer cases (p=0.59). Controls with current smoking status had a significantly higher NERC (mean+SD, 5.72+3.30, n=38) than never smokers (4.61+2.76, n=206). There was a significant association between lower NERC and elevated breast cancer risk only among current smokers (odds ratio [OR]=4.44; 95% confidence interval [CI]=1.03-19.13) after adjustment for age, race, and family history. In contrast, there was a significant association between lower NERC and reduced breast cancer risk in never smokers (OR=0.39; 95%CI=0.20-0.76). In controls, smoking-related elevation of NERC may be related to adaptive response. In breast cancer cases, elevated cancer risk may be associated with: (1) deficient NER response to smoking-related DNA damages in smokers and (2) environmental exposures (e.g. ionizing radiation) in non-smokers, which induced NER but repaired by other repair pathways (e.g. base excision and double-strand repair). Our findings highlight the complex interplay between individual's NER capacity and smoking in breast cancer risk. Citation Format: Jennifer J. Hu, Glenn O. Allen, Isildinha M. Reis, Feng Gong. Interactions between smoking and DNA repair in breast cancer risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4834. doi:10.1158/1538-7445.AM2013-4834
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