Lee Kyoung-Mu, Choi Ji-Yeob, Lee Jong Eun, Noh Dong-Young, Ahn Sei-Hyun, Han Wonshik, Yoo Keun-Young, Hayes Richard B, Kang Daehee
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Breast Cancer Res Treat. 2007 Dec;106(3):433-8. doi: 10.1007/s10549-007-9506-y. Epub 2007 Jan 30.
Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case-control study conducted in Korea. We recruited 1,385 eligible patients with histologically confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (-786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the -786T > C or 894G > T genotype and breast cancer risk. However, the -786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56-1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59-0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women.
内皮型一氧化氮合酶（NOS3）产生一氧化氮，而一氧化氮是一种可能与乳腺癌相关的细胞毒性作用介质。我们在韩国进行了一项病例对照研究，评估了NOS3基因多态性在乳腺癌病因学中的作用。我们招募了1385例经组织学确诊的新发乳腺癌患者和968例基于医院的对照。对启动子区域（-786T>C）和外显子7（894G>T，Glu298Asp）中的两个潜在功能性NOS3多态性进行基因分型，并估计个体单倍型。通过无条件逻辑回归计算比值比（OR）和95%置信区间（95%CI），并对年龄、体重指数、教育程度、一级和二级亲属的乳腺癌家族史、首次足月妊娠年龄和产次进行调整。-786T>C或894G>T基因型与乳腺癌风险之间没有总体关联。然而，-786C等位基因与伴有淋巴结受累的浸润性乳腺癌风险降低存在微弱关联（OR=0.76，95%CI=0.56-1.04）。并且，与TG-TG携带者相比，所有其他单倍型对均与伴有淋巴结受累的浸润性乳腺癌显著相关（OR=0.77，95%CI=0.59-0.99）。我们的结果表明，NOS3基因多态性可改变韩国女性对伴有淋巴结受累的浸润性乳腺癌的个体易感性。
