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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.

Publication ,  Journal Article
Lu, J; Wei, Q; Bondy, ML; Yu, T-K; Li, D; Brewster, A; Shete, S; Sahin, A; Meric-Bernstam, F; Wang, L-E
Published in: Cancer
November 1, 2006

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.

Duke Scholars

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

November 1, 2006

Volume

107

Issue

9

Start / End Page

2245 / 2253

Location

United States

Related Subject Headings

  • White People
  • Surveys and Questionnaires
  • Risk Factors
  • Reference Values
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Nitric Oxide Synthase Type III
  • Middle Aged
  • Humans
 

Citation

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Lu, J., Wei, Q., Bondy, M. L., Yu, T.-K., Li, D., Brewster, A., … Wang, L.-E. (2006). 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. Cancer, 107(9), 2245–2253. https://doi.org/10.1002/cncr.22269
Lu, Jiachun, Qingyi Wei, Melissa L. Bondy, Tse-Kuan Yu, Donghui Li, Abenaa Brewster, Sanjay Shete, Aysegul Sahin, Funda Meric-Bernstam, and Li-E Wang. “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.Cancer 107, no. 9 (November 1, 2006): 2245–53. https://doi.org/10.1002/cncr.22269.
Lu J, Wei Q, Bondy ML, Yu T-K, Li D, Brewster A, Shete S, Sahin A, Meric-Bernstam F, Wang L-E. 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. Cancer. 2006 Nov 1;107(9):2245–2253.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

November 1, 2006

Volume

107

Issue

9

Start / End Page

2245 / 2253

Location

United States

Related Subject Headings

  • White People
  • Surveys and Questionnaires
  • Risk Factors
  • Reference Values
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Nitric Oxide Synthase Type III
  • Middle Aged
  • Humans