Genetic Polymorphisms of eNOS, Hormone Receptor Status, and Survival of Breast Cancer

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.