Download PDF
CC BY 4.0 · Glob Med Genet 2020; 07(04): 121-127
DOI: 10.1055/s-0041-1722952
Original Article

Impact of ERCC2 Gene Polymorphisms on OSCC Susceptibility and Clinical Characteristics

ML Avinash Tejasvi
1   Department of Oral Medicine and Radiology, Kamineni Institute of Dental sciences, Narketpally, Saveetha University, Chennai, India
,
Gopal Maragathavalli
2   Department of Oral Medicine and Radiology, Saveetha Dental College and Hospitals, Chennai, India
,
Putcha Uday Kumar
3   Department of Pathology & Microbiology, National Institute of Nutrition, Hyderabad, India
,
M. Ramakrishna
4   Department of Radiation Oncology, MNJ Institute of Oncology & Regional Cancer Centre, Hyderabad, India
,
Vijaya Raghavan
5   Department of Research and Development, Saveetha University, Chennai, India
,
Anulekha Avinash CK
6   Department of Prosthodontics, Kamineni Institute of Dental Sciences Narketpally, Telangana, India
› Author Affiliations
› Further Information
   Permissions and Reprints

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.

Keywords

oral cancer - ERCC2 - DNA repair - platinum-based chemotherapy


Publication History

Article published online:
18 February 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Huang X, Gao Y, He J. et al. The association between RFC1 G80A polymorphism and cancer susceptibility: evidence from 33 studies. J Cancer 2016; 7 (02) 144-152
    CrossrefPubMedGoogle Scholar
  • 2 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (05) 646-674
    CrossrefPubMedGoogle Scholar
  • 3 Biason P, Hattinger CM, Innocenti F. et al. Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. Pharmacogenomics J 2012; 12 (06) 476-483
    CrossrefPubMedGoogle Scholar
  • 4 Simon GR, Ismail-Khan R, Bepler G. Nuclear excision repair-based personalized therapy for non-small cell lung cancer: from hypothesis to reality. Int J Biochem Cell Biol 2007; 39 (7-8): 1318-1328
    CrossrefPubMedGoogle Scholar
  • 5 Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis. Int J Med Sci 2007; 4 (02) 59-71
    CrossrefPubMedGoogle Scholar
  • 6 Weber CA, Salazar EP, Stewart SA, Thompson LH. ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. EMBO J 1990; 9 (05) 1437-1447
    CrossrefPubMedGoogle Scholar
  • 7 Chen JZ, Kadlubar FF. A new clue to glaucoma pathogenesis. Am J Med 2003; 114 (08) 697-698
    CrossrefPubMedGoogle Scholar
  • 8 Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM. Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet 1998; 20 (02) 184-188
    CrossrefPubMedGoogle Scholar
  • 9 Mitra AK, Singh N, Garg VK, Chaturvedi R, Sharma M, Rath SK. Statistically significant association of the single nucleotide polymorphism (SNP) rs13181 (ERCC2) with predisposition to squamous cell carcinomas of the head and neck (SCCHN) and breast cancer in the north Indian population. J Exp Clin Cancer Res 2009; 28: 104
    CrossrefPubMedGoogle Scholar
  • 10 Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S. Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature 1993; 365 (6449): 852-855
    CrossrefPubMedGoogle Scholar
  • 11 Friedberg EC. How nucleotide excision repair protects against cancer. Nat Rev Cancer 2001; 1 (01) 22-33
    CrossrefPubMedGoogle Scholar
  • 12 Benhamou S, Sarasin A. ERCC2/XPD gene polymorphisms and cancer risk. Mutagenesis 2002; 17 (06) 463-469
    CrossrefPubMedGoogle Scholar
  • 13 Lunn RM, Helzlsouer KJ, Parshad R. et al. XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 2000; 21 (04) 551-555
    CrossrefPubMedGoogle Scholar
  • 14 Hou SM, Fält S, Angelini S. et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 2002; 23 (04) 599-603
    CrossrefPubMedGoogle Scholar
  • 15 Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003; 111 (15) 1843-1850
    CrossrefPubMedGoogle Scholar
  • 16 Spitz MR, Wu X, Wang Y. et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001; 61 (04) 1354-1357
    PubMedGoogle Scholar
  • 17 Bau DT, Wu HC, Chiu CF. et al. Association of XPD polymorphisms with prostate cancer in Taiwanese patients. Anticancer Res 2007; 27 (4C): 2893-2896
    Google Scholar
  • 18 Li M, Zhao Y, Zhao E, Wang K, Lu W, Yuan L. Predictive value of two polymorphisms of ERCC2, rs13181 and rs1799793, in clinical outcomes of chemotherapy in gastric cancer patients: a meta-analysis. Dis Markers 2018; 2018: 3947626
    PubMedGoogle Scholar
  • 19 Vella N, Aiello M, Russo AE. et al. ‘Genetic profiling’ and ovarian cancer therapy (review). Mol Med Rep 2011; 4 (05) 771-777
    PubMedGoogle Scholar
  • 20 Smolarz B, Makowska M, Samulak D. et al. Single nucleotide polymorphisms (SNPs) of ERCC2, hOGG1, and XRCC1 DNA repair genes and the risk of triple-negative breast cancer in Polish women. Tumour Biol 2014; 35 (04) 3495-3502
    CrossrefPubMedGoogle Scholar