title: Genetic polymorphisms of NOS3 are associated with the risk of invasive breast cancer with lymph node involvement.
abstract: Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case-control study conducted in Korea. We recruited 1,385 eligible patients with histologically confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (-786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the -786T > C or 894G > T genotype and breast cancer risk. However, the -786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56-1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59-0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.forename: Jong Eun
authors.initials: JE
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: Wonshik
authors.initials: W
authors.lastname: Han
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; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III