title: Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer.
abstract: 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.
authors.affiliation: Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Sang-Goo
authors.initials: SG
authors.lastname: Shin
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D052250:Nitric Oxide Synthase Type III