Carcinogenesis Advance Access originally published online on January 27, 2007
Carcinogenesis 2007 28(6):1247-1253; doi:10.1093/carcin/bgm016
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Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA, 1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
2 Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA 30329, USA
* To whom correspondence should be addressed at Virginia Department of Health, Office of Epidemiology, James Madison Building, Room 532A, 109 Governor Street, Richmond, VA 23219, USA. Tel: +1 804 864 8140; Fax: +1 804 864 8139; Email: jun.yang{at}vdh.virginia.gov
NOS3 and MPO genes 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 that NOS3 and MPO polymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations between NOS3 Glu298Asp and MPO G-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 for NOS3 and MPO was 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 between NOS3 and MPO genotypes and breast cancer risk. When considering smoking, variant NOS3 genotypes (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 >10 cigarettes per day (OR = 2.19, 95% CI = 1.21–3.97). NOS3 genotypes 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.
Abbreviations: CI, confidence intervale; NOS, endothelial nitric oxide synthase; MPO, myeloperoxidase; NO, nitric oxide; OR, odds ratio; ROS, reactive oxygen species
Received October 12, 2006; revised December 26, 2006; accepted January 16, 2007.
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