Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study.

Saniya Nissar,Aga Syed Sameer,Roohi Rasool,Nissar A Chowdri,Fouzia Rashid

doi:10.7314/apjcp.2015.16.15.6385

Abstract

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p<0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

Highlights

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancerrelated death in many parts of the Western world (Gellad and Provenzale, 2010)
Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population
Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancerrelated death in many parts of the Western world (Gellad and Provenzale, 2010). In mammalian cells four different DNA repair mechanisms have been identified: base excision repair (BER), nucleotide excision repair (NER), double-strand break repair and mismatch repair (Yu et al, 1999, Christmann et al, 2003) All these DNA repair pathways are finely regulated for the maintenance of genomic integrity and modulation of repair capacity in response to DNA damage and susceptibility to CRC (Naccarti et al, 2007). Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population

Methods

Results

Conclusion