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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.
Cancer 2006; 107(9):2245-53C

Abstract

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.

Authors+Show Affiliations

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17063466

Citation

Lu, Jiachun, et al. "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, vol. 107, no. 9, 2006, pp. 2245-53.
Lu J, Wei Q, Bondy ML, et al. 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;107(9):2245-53.
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), pp. 2245-53.
Lu J, et al. 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):2245-53. PubMed PMID: 17063466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lu,Jiachun, AU - Wei,Qingyi, AU - Bondy,Melissa L, AU - Yu,Tse-Kuan, AU - Li,Donghui, AU - Brewster,Abenaa, AU - Shete,Sanjay, AU - Sahin,Aysegul, AU - Meric-Bernstam,Funda, AU - Wang,Li-E, PY - 2006/10/26/pubmed PY - 2006/12/21/medline PY - 2006/10/26/entrez SP - 2245 EP - 53 JF - Cancer JO - Cancer VL - 107 IS - 9 N2 - 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. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/17063466/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_ L2 - https://doi.org/10.1002/cncr.22269 DB - PRIME DP - Unbound Medicine ER -