Genotypic analysis of XRCC4 and susceptibility to cervical cancer.

Background: XRCC4 encodes a DNA repair protein which maintains genome stability by repairing double-strand breaks by the error-prone method. Defects in the protein-encoding gene lead to impairment of DNA repair process and accumulation of DNA damage, a hallmark of cancer development. We hypothesised that variants in XRCC4 are linked to cervical cancer.Material and methods: Genotyping of XRCC4 variants viz. intron3 DIP (rs28360071), intron7 DIP (rs28360017), G-1394T(rs6869366) and G-652T (rs2075685) was carried out in 246 women with cervical cancer cases and 246 control women.Results: There were several links to cervical cancer: intron3 DIP (rs28360071) II genotype (p = 0.002) and I allele (odds ratio is 0.54-0.89) (p = 0.004), intron7 DIP (rs28360017) II genotype (p = 0.003) and I allele (odds ratio 0.68 [0.53-0.88]) (p = 0.004), and G-652T (rs2075685) genotype (p = 0.044) and the T allele (odds ratio 1.35 [1.03-1.77]) (p = 0.032). In combining data into haploviews, the DDGG allele combination had an odds ratio of 0.12 (0.04-0.39) (p= 0.029) and the IIGT combination an odds ratio of 3.08 (1.25-7.55) (p = 0.01) for cervical cancer.Conclusion: Our results suggested that homozygous 'I' and 'T' genotypes in certain XRCC4 sequences may be associated with the development of cervical cancer and so may be a useful biomarker to predict cervical cancer susceptibility.

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