Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk
Received 8 October 2019
Accepted for publication 4 February 2020
Published 16 March 2020 Volume 2020:13 Pages 73—86
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Wing-Kin Syn
Jagjeet Kaur, 1 Vasudha Sambyal, 1 Kamlesh Guleria, 1 Neeti Rajan Singh, 2 Manjit Singh Uppal, 2 Mridu Manjari, 3 Meena Sudan 4
1Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University, Amritsar, India; 2Department of Surgery; 3Department of Pathology; 4Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India
Correspondence: Vasudha Sambyal
Department of Human Genetics, Guru Nanak Dev University, Amritsar 143001, Punjab, India
Tel +911832258803-09 ext 3448
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, r 2=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
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