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Genetic Polymorphisms of Selected DNA Repair Genes, Estrogen and Progesterone Receptor Status, and Breast Cancer Risk

Authors' Affiliations: Departments of ¹ Preventive Medicine, ² General Surgery, Cancer Research Institute, and ³ Microbiology and Immunology, Seoul National University College of Medicine; ⁴ Institute of Environmental Medicine, SNUMRC; ⁵ Department of Surgery, Ulsan University College of Medicine, Seoul, Korea; ⁶ Department of Biological Sciences, KAIST, Daejeon, Korea; ⁷ Department of Preventive Medicine, Konkuk University College of Medicine, Chuncheongbuk-Do, Korea; ⁸ Clinical Research Institute, Labgenomics Co., Ltd., Doosan Engineering Center, Kyungki-Do, Korea; and ⁹ Department of Epidemiology, The University of Texas, M.D.Anderson Cancer Center, Houston, Texas

Requests for reprints: Daehee Kang, Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799, Korea. Phone: 82-2-740-8326; Fax: 82-2-747-4830; E-mail: dhkang{at}snu.ac.kr.

Purpose: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women.

Experimental Design: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg¹⁸⁸His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 –93G > A, and Ile²¹⁹Val).

Results: We found that the RAD52 2259 CT or TT, hMLH1 –93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferroni's method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor–negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively).

Conclusion: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.

Key Words: breast cancer • genetic polymorphism • DNA repair • estrogen receptor • progesterone receptor

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