Genetic Polymorphisms of Ataxia Telangiectasia Mutated and Breast Cancer Risk

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2005-04, Vol.14 (4), p.821-825
• Main Authors: LEE, Kyoung-Mu, CHOI, Ji-Yeob, WEI, Qingyi, KANG, Daehee, PARK, Sue Kyung, CHUNG, Hye-Won, AHN, Byungchan, YOO, Keun-Young, HAN, Wonshik, NOH, Dong-Young, AHN, Sei-Hyun, KIM, Ho
• Format: Article
• Language: English
• Subjects: Ataxia Telangiectasia Mutated Proteins; ATM; Bayes Theorem; Biological and medical sciences; breast cancer; Breast Neoplasms - etiology; Breast Neoplasms - genetics; Case-Control Studies; Cell Cycle Proteins - genetics; DNA-Binding Proteins - genetics; Female; genetic polymorphism; Gynecology. Andrology. Obstetrics; haplotype; Haplotypes; Humans; Korea; Mammary gland diseases; Medical sciences; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide - genetics; Postmenopause; Premenopause; Protein-Serine-Threonine Kinases - genetics; Risk Factors; Tropical medicine; Tumor Suppressor Proteins - genetics; Tumors
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-04-0330

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 (χ 2 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