Genetic polymorphisms of ATM and breast cancer risk
Authors: Kyoung-Mu Lee, Ji-Yeob Choi, Sue Kyung Park, Hye-Won Chung, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Daehee Kang
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1495 

To evaluate the role of genetic polymorphisms of ATM (ataxia telangiectasia mutated) in breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n=990) and controls (n=1185) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995-2003. Information on demographic characteristics and other information were collected by interviewed questionnaire. Those polymorphic sites of which the variant allele frequencies are more than 10% were selected for analysis. Genotypes of ATM -5144A>T ([rs228589][1]), 3393T>G (rs4585), IVS21+1049T>C ([rs664677][2]), IVS33-55T>C ([rs664982][3]), and IVS34+60G>A ([rs664143][4]) were determined by 5′-nuclease assay (TaqMan). Linkage disequilibrium and haplotype frequencies were estimated from genotype data using EH program. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusting for age, education, family history of breast cancer, parity, age at first full-term pregnancy, alcohol consumption and smoking. Allele frequencies (-5144A: 0.48, 3393T: 0.46, IVS21+1049T: 0.41, IVS33-55T: 0.46, and IVS34+60G: 0.47) were higher or lower than those (0.33, 0.64, 0.66, 0.66, 0.66) in Caucasian. These alleles were found to be in linkage disequilibrium (p<0.001). The most prevalent haplotype was T-G-C-C-A in both cases (50.2%) and controls (50.8%). The haplotype frequencies of A-T-T-T-G (cases: 34.3% vs. controls: 38.8%), A-T-C-T-G (6.5% vs. 5.9%), A-G-C-C-A (2.1% vs. 1.4%), and A-T-T-C-G (1.7% vs. 0.7%) were significantly different between cases and controls (χ2-test: p<0.001). The IVS21+1049 TC or CC genotype and the IVS34+60 GA or AA genotype increased the risk (OR=1.35, 95% CI=1.06-1.72 and OR=1.25, 95% CI=1.00-1.55, respectively), particularly in premenopausal women (OR=1.44, 95% CI=1.06-1.97 and OR=1.35, 95% CI=1.02-1.78, respectively). Those women with combined genotypes of AA-TT-TT-TT-GG (case: 12.4% vs. control: 16.6%) had the moderately decreased risk of breast cancer compared with those with the most prevalent combined genotypes (AT-TG-TC-CT-AG; case: 35.9% vs. control: 37.7%) (OR=0.79, 95% CI=0.60-1.04). On the other hand, those women with AT-TG-TC-CC-GA (case: 3.2% vs. control: 1.3%) and AA-TG-TC-TC-GA (case: 2.0% vs. control: 1.4%) genotype had the increased risk compared with those with the most prevalent one (OR=2.30, 95% CI=1.20-4.47 and OR=2.44, 95% CI=1.08-5.51, respectively). Premenopausal breast cancer risk for smokers (≥400 cigarettes/lifetime) with non AA-TT-TT-TT-GG genotype was 2.2-fold increased compared with nonsmokers with AA-TT-TT-TT-GG genotype (95% CI=1.26-3.87), suggesting the more than additive interactive effect between smoking and ATM genotypes on premenopausal breast cancer risk. Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women.

 [1]: /lookup/external-ref?link_type=GEN&access_num=rs228589&atom=%2Fcanres%2F64%2F7_Supplement%2F344.2.atom
 [2]: /lookup/external-ref?link_type=GEN&access_num=rs664677&atom=%2Fcanres%2F64%2F7_Supplement%2F344.2.atom
 [3]: /lookup/external-ref?link_type=GEN&access_num=rs664982&atom=%2Fcanres%2F64%2F7_Supplement%2F344.2.atom
 [4]: /lookup/external-ref?link_type=GEN&access_num=rs664143&atom=%2Fcanres%2F64%2F7_Supplement%2F344.2.atom