Impact of ERCC2 Gene Polymorphisms on OSCC Susceptibility and Clinical Characteristics.

Gopal Maragathavalli,Anulekha Avinash Ck,Ml Avinash Tejasvi,Putcha Uday Kumar,M Ramakrishna,Vijaya Raghavan

doi:10.1055/s-0041-1722952

Abstract

Background DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer. Objectives This study aimed to investigate the association between Excision repair cross-complementation groups 2 (ERCC2) single nucleotide polymorphisms (SNPs rs1799793 and rs13181) and the response to platinum-based chemotherapy among patients with oral squamous cell carcinoma (OSCC). Methodology Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism from a total of 150 OSCC patients and 150 normal tissues of same patients were collected as controls for this study. Results ERCC2 GA (Asp312Asn) AC (Lys751Gln) genotypes were significantly associated ( p = 0.0001 and p = 0.0004, respectively) with OSCC patients, when compared with the controls. These findings suggest that potentially functional SNPs in ERCC2 may contribute to OSCC risk. This study highlights the genetic variant that might play a role in mediating susceptibility to OSCC in this population. An understanding of DNA repair gene polymorphisms might not only enable risk assessment, but also response to therapy, which target the DNA repair pathway.

Highlights

Cancer describes a group of diseases characterized by the uncontrolled growth and spread of abnormal cells
This study aimed to investigate the association between Excision repair cross-complementation groups 2 (ERCC2) single nucleotide polymorphisms (SNPs rs1799793 and rs13181) and the response to platinum-based chemotherapy among patients with oral squamous cell carcinoma (OSCC)
Many of the ages mentioned in case sheets or given by patients were arbitrary, exact age of 150 OSCC patients and 150 controls was available, analysis was performed with those, mean age at which OSCC was identified as 9–87/49.30 Æ 15.55 in males and 27–75/84.20 Æ 11.26 in females years

Summary

Introduction

Cancer describes a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. The nucleotide excision repair (NER) pathway, a highly powerful and sophisticated DNA damage removal pathway, has been believed to play important roles in cancer progression and response to platinum-based chemotherapy.[3,4] Excision repair cross-complementation groups 2 (ERCC2) are gene encoding one of the key enzymes in NER pathway.[5] ERCC2 gene, called the xeroderma pigmentosum group D (XPD) gene, is located at chromosome 19q13.3. It comprises of 23 exons and spans approximately 54,000 base pairs.[6] It is an important component of the transcription factor IIH that is involved in NER of UV-induced damage and removal of bulky adducts.[7]. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer

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Conclusion