Yang Jun, Ambrosone Christine B, Hong Chi-Chen, Ahn Jiyoung, Rodriguez Carmen, Thun Michael J, Calle Eugenia E
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Carcinogenesis. 2007 Jun;28(6):1247-53. doi: 10.1093/carcin/bgm016. Epub 2007 Jan 27.
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.
NOS3基因和MPO基因分别编码内皮型一氧化氮合酶和髓过氧化物酶（MPO），它们可产生一氧化氮和活性氧。由于吸烟会产生活性物质，我们推测NOS3和MPO基因多态性可能会影响患乳腺癌的易感性，尤其是在吸烟者中。我们在美国癌症协会的癌症预防研究II营养队列中的绝经后女性中，研究了NOS3 Glu298Asp和MPO G - 463A基因多态性与吸烟导致的乳腺癌风险之间的关联。该分析纳入了502名在1992年至2001年间提供血液样本并被诊断为乳腺癌的女性，以及505名年龄、种族/民族和献血日期与病例匹配的无癌对照。使用TaqMan进行NOS3和MPO基因分型，并采用无条件逻辑回归计算比值比（OR）和95%置信区间（CI）。未发现NOS3和MPO基因分型与乳腺癌风险之间存在统计学显著关系。在考虑吸烟因素时，NOS3基因变异型（GT和TT）在从不吸烟者中与降低的乳腺癌风险显著相关（OR = 0.67，95% CI = 0.45 - 0.99），但在曾经吸烟者中与较高风险相关（OR = 1.59，95% CI = 1.05 - 2.41），对于每天吸烟超过10支的人，风险增加2倍（OR = 2.19，95% CI = 1.21 - 3.97）。NOS3基因分型似乎与吸烟者绝经后乳腺癌风险相关，支持了基于基因特征的女性亚组在接触烟草烟雾时可能患乳腺癌风险更高的假设。
