Choi Ji-Yeob, Lee Kyoung-Mu, Noh Dong-Young, Ahn Sei-Hyun, Lee Jong-Eun, Han Wonshik, Jang In-Jin, Shin Sang-Goo, Yoo Keun-Young, Hayes Richard B, Kang Daehee
Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Breast Cancer Res Treat. 2006 Nov;100(2):213-8. doi: 10.1007/s10549-006-9245-5. Epub 2006 Jul 4.
The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS -786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995-2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS -786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03-4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95-10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85-3.93). The combined genotypes containing -786C or 894T was associated with a 2.5-fold risk, compared to the TT-GG genotypes, the most dominant genotype combination (95% CI = 1.29-4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31-18.36). These results indicate that the eNOS -786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors.
内皮细胞特异性一氧化氮合酶（eNOS）可能通过血管生成或细胞凋亡在肿瘤进展中发挥重要作用。我们研究了eNOS的两个功能上具有重要意义的单核苷酸多态性（SNP），即-786T>C和894G>T（Glu298Asp），与1995年至2002年从韩国首尔的两家教学医院招募的873例新发、非转移性乳腺癌女性患者的乳腺癌复发或死亡风险的关系。通过Cox比例风险模型估计风险，与基因型相关，并根据激素受体状态、淋巴结受累情况和肿瘤大小进行调整。与TT基因型的女性相比，携带eNOS -786C等位基因的女性乳腺癌复发或死亡风险显著增加（风险比[HR]=2.1，95%置信区间[CI]=1.03-4.33）；在雌激素受体（ER）阳性病例中，风险增加高达3倍（HR=3.2，95%CI=0.95-10.50）。eNOS 894T携带者的风险也有所增加，然而，未达到统计学显著性（HR=1.8，95%CI=0.85-3.93）。与最主要的基因型组合TT-GG相比，含有-786C或894T的联合基因型的风险增加了2.5倍（95%CI=1.29-4.68），在ER阳性病例中风险最高（HR=4.9，95%CI=1.31-18.36）。这些结果表明，eNOS -786C多态性，可能还有894T多态性，与乳腺癌复发和死亡相关，特别是在ER阳性肿瘤的女性中。
