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NOS3andMPOgenes encode endothelial nitric oxide synthase and myeloperoxidase (MPO), respectively, which generate nitric oxide and reactive oxygen species. Because cigarette smoking generates reactive species, we hypothesized thatNOS3andMPOpolymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations betweenNOS3Glu298Asp andMPOG-463A polymorphisms and breast cancer risk by cigarette smoking among post-menopausal women in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Included in this analysis were 502 women who provided blood samples and were diagnosed with breast cancer between 1992 and 2001 and 505 cancer-free controls who were matched to the cases by age, race/ethnicity and date of blood donation. Genotyping forNOS3andMPOwas performed using TaqMan, and unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). No statistically significant relationships were found betweenNOS3andMPOgenotypes and breast cancer risk. When considering smoking, variantNOS3genotypes (GT and TT) were significantly associated with reduced breast cancer risk among never smokers (OR = 0.67, 95% CI = 0.45–0.99), but were associated with higher risk among ever smokers (OR = 1.59, 95% CI = 1.05–2.41) and 2-fold increase in risk for those who smoked &gt;10 cigarettes per day (OR = 2.19, 95% CI = 1.21–3.97).NOS3genotypes appeared to be associated with risk of post-menopausal breast cancer among smokers, supporting the hypothesis that subgroups of women based upon genetic profiles may be at higher risk of breast cancer when exposed to tobacco smoke.

carcinogenesis

Relationships between polymorphisms in               NOS3               and               MPO               genes, cigarette smoking and risk of post-menopausal breast cancer