Promoter polymorphism (-786t>C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non-Hispanic white women age younger than 55 years.
BACKGROUND
Nitric oxide (NO) is constitutively synthesized in the endothelium by endothelial nitric oxide synthase (eNOS) and acts as a pleiotropic regulator involved in carcinogenesis. Most breast cancers develop from mammary epithelial cells; therefore, NO may play a role in their development. It was hypothesized that eNOS polymorphisms are associated with risk of breast cancer.


METHODS
In the current hospital-based case-control study of 421 non-Hispanic white women with sporadic breast cancer and 423 frequency-matched control subjects, we genotyped 3 polymorphisms of eNOS (i.e., -786T>C, the 27-base pair [bp] variable number of tandem repeats [VNTR] in intron 4, and 894G>T [Glu298Asp]) and assessed their associations with risk of breast cancer.


RESULTS
It was found that, compared with -786TT, the -786C variant genotypes were associated with a significantly increased risk of breast cancer in an allele dose-dependent manner (adjusted odds ratio [OR], 1.33 [95% confidence interval (95% CI)], 0.99-1.77 for -786TC; and OR, 1.79 [95% CI, 1.11-2.87] for -786CC; P(trend) = .007), but 27-bp VNTR and 894G>T genotypes were not. Stratification analysis demonstrated that the risk associated with -786C variant genotypes (-786TC/CC) was more pronounced in smokers and in those 50 years or older (OR, 1.82 [95% CI, 1.19-2.80] and OR, 2.08 [95% CI, 1.25-3.45], respectively), and in the estrogen and progesterone receptor-negative cases (OR, 1.70 [95% CI, 1.10-2.62] and OR, 1.57 [95% CI, 1.07-2.32], respectively). Furthermore, the C4G haplotype derived from the observed genotypes was also associated with a significantly increased risk of breast cancer (OR, 2.16; 95% CI, 1.07-4.36).


CONCLUSIONS
The results suggest that eNOS polymorphisms (especially -786T>C) may play a role in the development of sporadic breast cancer.
Lu
Jiachun
J
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Wei
Qingyi
Q
Bondy
Melissa L
ML
Yu
Tse-Kuan
TK
Li
Donghui
D
Brewster
Abenaa
A
Shete
Sanjay
S
Sahin
Aysegul
A
Meric-Bernstam
Funda
F
Wang
Li-E
LE
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D004727:Endothelium / Q000201:enzymology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012307:Risk Factors; D011795:Surveys and Questionnaires; D044465:White People / Q000235:genetics
D052250:Nitric Oxide Synthase Type III