Abstract 2601: Polymorphisms in oxidative stress genes, physical activity and breast cancer risk
Authors: Lauren E. McCullough, Marilie D. Gammon, Rebecca J. Cleveland, Patrick T. Bradshaw, Robert C. Millikan, Kari E. North, Andrew F. Olshan, Sybil M. Eng, Christine B. Ambrosone, Jiyoung Ahn, Susan E. Steck, Mia M. Gaudet, Susan L. Teitelbaum, Alfred I. Neugut
Journal: Cancer Research (2012)

Abstract BACKGROUND. Reactive oxygen species (ROS) are known to react with DNA resulting in the transformation of normal epithelium to a malignant phenotype. While one functional variant in catalase (CAT) has been shown to be pertinent to breast cancer risk, few other polymorphisms in this gene have been assessed. Genetic variation in CAT or other genes in the oxidative stress pathway may mediate the carcinogenic effect of ROS produced by recreational physical activity (RPA) or result in adaptation of antioxidant capacity. METHODS. We investigated the association between three polymorphisms in CAT (rs4756146, rs2284365, rs480575) and breast cancer risk. We also characterized the joint effects of RPA with CAT, and with other functional oxidative stress variants (COMT, GPX, GSTA1, GSTM1, GSTP1, GSTT1, MnSOD, MPO, and UGT2B7) on breast cancer risk. Data were from the Long Island Breast Cancer Study Project, a population-based case-control study with interview and biomarker data available on 1102 cases and 1141 controls. Adjusted unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS. The presence of at least one CAT variant allele in rs4756146 was associated with a 23% decreased risk of postmenopausal breast cancer (95% CI=0.59-0.99). While rs2284365 and rs480575 were not associated with breast cancer risk, interaction between the two was evident on the multiplicative scale (likelihood ratio test p=0.087) indicating possible antagonism for these CAT polymorphisms. Further, upon combining the CAT genotypes, we observed a positive association between breast cancer risk and the number of putative high-risk alleles. Women with ≤ 4 high-risk alleles were at a 44% increased risk of breast cancer (95% CI=1.04-2.00) compared to women with ≤ 2 high-risk alleles. Finally, two polymorphisms (CAT rs1001179 and GSTP1 rs1695) among the oxidative stress genes considered were found to interact multiplicatively with postmenopausal RPA. Variant alleles in CAT antagonistically reversed the effect of high RPA on breast cancer risk (p=0.043) while variant alleles in GSTP1 synergistically enhanced the effect of low RPA on breast cancer risk (p=0.006). CONCLUSIONS. This study suggests that postmenopausal breast cancer risk may be decreased among women with one variant CAT allele in rs4756146. Risk may be elevated when considering combined effects of multiple high risk alleles in CAT. Variants in both CAT and GSTP1 may modify the association between RPA and breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2601. doi:1538-7445.AM2012-2601