title: Genetic polymorphisms of ataxia telangiectasia mutated and breast cancer risk.
abstract: To evaluate the role of genetic polymorphisms of ataxia telangiectasia mutated (ATM) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the ATM polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five ATM alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The ATM IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women.
authors.affiliation: Department of Preventive Medicine, Cancer Research Institute, Seoul National University, College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799, Korea.
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.forename: Sue Kyung
authors.initials: SK
authors.lastname: Park
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Chung
authors.forename: Byungchan
authors.initials: B
authors.lastname: Ahn
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007723:Korea; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause; D017697:Premenopause; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases