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The XRCC3 Thr241Met polymorphism and breast cancer risk: a case-control study in a Thai population
Authors:Suleeporn Sangrajrang  Peter Schmezer  Iris Burkholder  Paolo Boffetta  Paul Brennan  Andreas Woelfelschneider  Helmut Bartsch  Surapon Wiangnon  Arkom Cheisilpa  Odilia Popanda
Institution:  a Research Division, National Cancer Institute, Bangkok, Thailand b Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany c Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany d International Agency for Research on Cancer (IARC), Lyon, France e Faculty of Medicine of Khon Kaen University, Thailand
Abstract:The X-ray repair cross-complementing group 3 gene (XRCC3) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted 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 were calculated for the entire population as well as for pre- and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02-2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95-3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82-2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry.
Keywords:Breast cancer  DNA repair  genetic polymorphism  XRCC3
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