Genotypic analysis of XRCC4 and susceptibility to cervical cancer

ABSTRACT

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

KEYWORDS:

• Cervical cancer
• disease susceptibility
• DNA repair
• genotyping
• SNPs
• XRCC4

Acknowledgements

The authors would like to thank Indian Council of Medical Research (ICMR), New Delhi, India and Centre of Excellence, Higher Education, Government of Uttar Pradesh, Lucknow, India for funding the work. MKG is thankful to Indian Council of Medical Research for Senior Research Fellowship (No: 3/1/3/WL/JRF-2011/HRD). The departmental equipment facility provided by UGC-SAP and DST-FIST-PURSE, New Delhi is duly acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Indian Council of Medical Research, New Delhi.