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Association of Polymorphisms in Base Excision Repair Genes With the Risk of Breast Cancer: A Case-Control Study in North Indian Women

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Inheritance of common genetic variants at one or more base excision repair (BER) genes may result in a reduced DNA repair capacity and in an increased risk of cancers like breast cancer. The present case-control study with 390 north Indian women (155 breast cancer cases and 235 controls) was aimed to investigate the association of seven nonsynonymous BER gene polymorphisms viz. rs1130409/T1865G (APEX1), rs1799782/T22142C (XRCC1), rs25487/G23990A (XRCC1), rs4989588/T3337A (FEN1), rs4989586/G3259A (FEN1), rs4989587/C3315T (FEN1), and rs1050525/G6941T (PCNA) with breast cancer susceptibility. Statistically significant association with breast cancer risk was observed for rs1130409 homozygous mutant GG [odds ratio (OR) 3.35, 95% confidence interval (CI) 1.36‐8.26), heterozygous GT (OR 2.42, 95% CI 1.56‐3.76), and combined mutant (GT + GG) (OR 2.52, 95% CI 1.65‐3.86] genotypes and rs25487 homozygous mutant AA (OR 2.91, 95% CI 1.66‐5.10) and combined mutant (AA + AG) (OR 1.41, 95% CI 0.903‐2.19) genotypes, whereas protective association was exhibited by rs1799782 homozygous mutant CC (OR 0.413, 95% CI 0.082‐2.08), heterozygous TC (OR 0.351, 95% CI 0.189‐0.650), and combined mutant (TC + CC) (OR 0.357, 95% CI 0.199‐0.641) genotypes. Association study using reconstructed haplotypes of XRCC1 gene showed positive association for the TA haplotype (OR 2.014, 95% CI 1.462‐2.775) and a protective association for the CG haplotype (OR 0.173, 95% CI 0.052‐0.576) pertaining to breast cancer risk. The results indicate that the polymorphisms rs1130409 (APEX1) and rs25487 (XRCC1) might be involved in contributing towards breast cancer susceptibility, while rs1799782 (XRCC1) might have protective influence.
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Keywords: Base excision repair (BER); Confidence interval; North Indian women; Odds ratio; Relative risk; Single nucleotide polymorphism (SNP)

Document Type: Research Article

Publication date: 01 March 2008

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