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Association of the genetic polymorphisms in XRCC6 and XRCC5 with the risk of ESCC in a high-incidence region of North China

Abstract

Background

The XRCC6 and XRCC5 genes are part of the nonhomologous end-joining (NHEJ) pathway, which is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. Genetic variations of XRCC6 and XRCC5 might contribute to esophageal squamous cell carcinoma (ESCC) susceptibility.

Methods

ESCC patients (n = 189) and cancer-free controls (n = 189) were recruited in an ESCC high-risk area of north China. Then the rs2267437 (XRCC6), rs3835 (XRCC5) and rs16855458 (XRCC5) polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

A significant difference in genotype distribution and allele frequency of rs2267437 (XRCC6) was observed between the cases and controls. The CG carriers were at higher risk of ESCC (p = 0.001, odds ratio [OR] = 2.040, 95% confidence interval [95% CI], 1.323-3.147). G allele carriers were also associated with an increased ESCC risk (p = 0.003, OR = 1.868, 95% CI, 1.230-2.836). In the 2 polymorphisms of XRCC5, no significant difference was found between both groups in the distribution of either genotype or allelic frequency. But in the haplotypes established by the single nucleotide polymorphisms (SNPs) of XRCC5, the haplotype AT and CC separately increased by 4.28- and 2.31-fold the risk ratio of ESCC (p = 0.01, OR = 4.28, 95% CI, 1.40-13.05; p = 0.03, OR = 2.31, 95% CI, 1.11-4.80, respectively). In addition, gene–smoking or gene–drinking interactions, and their effect on the risk of ESCC were observed, but no significant gene–environment interaction was demonstrated.

Conclusions

In conclusion, both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC susceptibility.

Tumori 2015; 101(1): 24 - 29

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/tj.5000206

Authors

Kun Li, Xiuli Yin, Hongli Yang, Jing Yang, Jianjian Zhao, Changqing Xu, Hongwei Xu

Article History

Disclosures

Financial support: This study was supported by the Program of Pharmaceutical Health and Technology Development of Shandong Province (No. HZ068), the Program of the National Science Foundation of Shandong Province (No. ZR2012HL20) and the Program of the National Science Foundation (No. 81200275).
Conflict of interest: The authors declare that they have no conflicts of interest.

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Authors

Affiliations

  • Medical School, Shandong University, Jinan - PR China
  • Department of Gastroenterology, Shandong Qianfoshan Hospital Affiliated to Shandong University, Jinan - PR China
  • Department of Internal Medicine, Shandong Rongjun Hospital, Jinan - PR China
  • Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan - PR China
  • K. Li and X. Yin contributed equally to this work

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