Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk

Abstract

Aim

The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high.

Methods

The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene–gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression.

Results

For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3–0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26–0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27–0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0–2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D̍́=0.845, r²=0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk.

Conclusion

XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.

Keywords:

• XRCC1
• XRCC2
• XRCC3
• polymorphisms
• esophageal cancer

Acknowledgments

We are grateful to the participants of the study. The research funding from UGC-UPE and UGC- SAP DRS II to Vasudha Sambyal and Kamlesh Guleria and research fellowship to Jagjeet Kaur is highly acknowledged.

Disclosure

The authors declare that they have no competing interests.