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Polymorphisms in three base excision repair genes and breast cancer risk in Thai women.
Sangrajrang S*, Schmezer P**, Burkholder I***,
Waas P**, Boffetta P****, Brennan P****,
Bartsch H**, Wiangnon S*****, and Popanda O**.
*Research Division, National Cancer Institute, Bangkok 10400, Thailand.
**Division of Toxicology and Cancer Risk Factors, German Cancer
Research Center (DKFZ), Heidelberg, Germany
***Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
****International Agency for Research on Cancer (IARC), Lyon, France
*****Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Email:sulee@health.moph.go.th
Abstract
DNA repair plays an important role in tumor development. The base excision repair (BER) pathway mainly removes DNA damage caused by ionizing radiation and reactive oxidative species. Here, we examined possible associations between polymorphisms in three important BER genes (OGG1 Ser326Cys, APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln) and breast cancer incidence in Thai women. The study population consisted of 507 breast cancer cases and 425 controls. Odds ratios (OR) were adjusted by multivariate logistic regression analysis for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education. For homozygous carriers of the Glu allele in APEX1, a significant protective effect was found when compared to Asp/Asp carriers (odds ratio (OR) = 0.60, 95% confidence interval (CI) = 0.38-0.94). Subgroup analysis based on menopausal status revealed increased breast cancer risk in postmenopausal women and OGG1 (OR = 2.05, 95% CI 1.14-3.69). Reconstructed diplotypes for XRCC1 showed that CGA/CGA carriers had an increased risk of breast cancer compared with carriers of the wild type diplotype CGG/CGG (OR = 2.56, 95% CI 1.28-5.15). When the joint effects of XRCC1, APEX1 and OGG1 polymorphisms were evaluated, individuals homozygous for two or three risk alleles were at increased risk (OR = 1.88, 95% CI 1.26-2.82). In conclusion, our data suggest that Thai women with a certain XRCC1 diplotype or homozygous for two or three variant alleles of XRCC1, OGG1, and APEX1 are likely to have an increased susceptibility to breast cancer.
Keywords : APEX1 - Case-control study - Menopausal status - OGG1 - Oxidative DNA damage - XRCC1
Breast Cancer Res Treat. 2008 Sep;111(2):279-88. Epub 2007 Oct 6.
