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.
Choi
Ji-Yeob
JY
Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Lee
Kyoung-Mu
KM
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Lee
Jong-Eun
JE
Han
Wonshik
W
Jang
In-Jin
IJ
Shin
Sang-Goo
SG
Yoo
Keun-Young
KY
Hayes
Richard B
RB
Kang
Daehee
D
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*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D052250:Nitric Oxide Synthase Type III