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OGG1 Polymorphisms and Breast Cancer Risk

Departments of ¹ Environmental Health Sciences and ² Epidemiology, Mailman School of Public Health, Columbia University; ³ Department of Community and Preventive Medicine, Mt. Sinai School of Medicine; ⁴ Pfizer, Inc., New York, New York; ⁵ Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, North Carolina; and ⁶ Laboratory of Genetic Ecotoxicology, Health Institute of Central Bohemia and Institute of Experimental Medicine AS CR, Prague, Czech Republic

Requests for reprints: Pavel Rossner, Jr., Institute of Experimental Medicine, LGE, Videnska 1083, Praha 4, Prague, Czech Republic. Phone: 420-24-106-2675; E-mail: prossner{at}biomed.cas.cz

The role of oxidative stress in breast cancer risk is still unclear. OGG1 encodes an 8-oxoguanine DNA glycosylase/AP lyase that catalyzes the removal of 8-oxodeoxyguanosine from DNA. 8-Oxodeoxyguanosine, the most abundant lesion generated by oxidative stress, is highly mutagenic. Environmental sources of oxidative stress, such as alcohol consumption, cigarette smoking, high body mass index (BMI), and low fruits and vegetables intake, may modify the association of genetic polymorphisms with breast cancer risk. We investigated the association between three genetic polymorphisms in OGG1 (Ser³²⁶Cys, 7143A/G, and 11657A/G) and breast cancer risk among 1,058 cases and 1,102 controls participating in the Long Island Breast Cancer Study Project. No associations were observed between individual OGG1 polymorphisms, haplotypes, or diplotypes and breast cancer. The association between having at least one variant allele and breast cancer risk was stronger among moderate alcohol drinkers for Ser³²⁶Cys [odds ratio (OR), 1.82; 95% confidence interval (95% CI), 1.06-3.10] relative to nondrinkers with the wild-type genotype and among those with higher BMI for 7143A/G (OR, 1.47; 95% CI, 1.10-1.96) and for 11657A/G (OR, 1.41; 95% CI, 1.05-1.88), relative to women with BMI < 25 kg/m² and the wild-type genotype. However, the patterns were not seen for all three single nucleotide polymorphisms (SNP) nor were there any clear allele dose associations; only one interaction was statistically significant, assuming a multiplicative model (11657A/G, P_interaction = 0.04). In summary, although we found some differences between the three OGG1 SNPs and breast cancer risk among moderate alcohol drinkers and women with higher BMI, replication of these results is needed to rule out spurious findings. In addition, data on functionality of these polymorphisms are crucial to understand if these modest differences are important. (Cancer Epidemiol Biomarkers Prev 2006;15(4):811–5)

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