Genetic polymorphism in DNA base excision repair gene XRCC1among medical radiation workers

Abstract

X-rays repair cross-complementing group 1 (XRCC1) gene is one of the gene that plays an important role in base excision repair system (BER) and DNA repair both single and double strand breaks. Individuals with XRCC1 exon 10 (Arg399Gln) gene polymorphisms and carrying 399Gln allele variants (A allele) have a greater risk of DNA damage than their wildtype, 399Arg. The aim of this study was to examine the genotype frequencies of single nucleotide polymorphisms (SNPs) of XRCC1 exon 10 among medical radiation workers. This study involved 77 samples from several hospitals in Indonesia. Genotyping of XRCC1 exon 10 gene polymorphism was performed using PCR-RFLP. Individuals carrying A allele had lower frequency than that is carrying their wildtype of 399Arg (0.39 vs. 0.61). The results indicated that 39% of medical radiation workers had a risk of repair efficiency of DNA damage and might influence an individual's risk of cancer. Ionizing radiation induces many types of damage to DNA, requiring multiple repair pathways to restore genomics integrity. Other important genes/pathways, especially those for DNA doublestrand break repair, might also play a role and should be further investigated. Furthermore, polymorphisms leading to inefficient DNA repair might also be associated with late reactions to radiotherapy. ABSTRAK Gen X-rays repair cross-complementing group1 (XRCC1) adalah salah satu gen yang berperan penting dalam BER dan perbaikan DNA baik kerusakan untai tunggal maupun ganda. Individu dengan polimorfisme gen XRCC1 exon 10 (Arg399Gln) dan membawa varian alel 399Gln (alel A) memiliki risiko kerusakan DNA lebih besar daripada wildtype, 399Arg. Tujuan dari penelitian ini adalah untuk menguji frekuensi genotip polimorfisme nukleotida tunggal (SNPs) dari XRCC1 exon 10 pada petugas radiasi medis. Penelitian ini melibatkan 77 sampel dari beberapa rumah sakit di Indonesia. Uji genotip polimorfisme gen XRCC1 ekson 10 dilakukan dengan menggunakan teknik PCR-RFLP. Individu yang membawa alel A memiliki frekuensi lebih rendah daripada yang membawa wildtype 399Arg (0,39 vs 0,61). Hasil ini menunjukkan bahwa 39% pekerja radiasi medis memiliki risiko berkurangnya efisiensi perbaikan kerusakan DNA dan dapat mempengaruhi risiko kanker seseorang. Radiasi pengion menginduksi berbagai jenis kerusakan pada DNA dan membutuhkan beberapa jalur perbaikan untuk memulihkan integritas genomik. Gen/jalur penting lainnya, terutama untuk perbaikan untai ganda DNA, mungkin juga berperan dan perlu diteliti lebih lanjut. Selanjutnya, polimorfisme yang menyebabkan perbaikan DNA yang tidak efisien juga terkait dengan respon terhadap radioterapi.

Association of XRCC1 genetic polymorphism with the risk of thyroid cancer in Indonesia

“…XRCC1 has three common SNPs, namely exon 6 (C>T) produces Arginine/Tryptophan substitution at codon 194, exon 9 (G>A) changes amino acids Arginine / Histidine at codon 280 and exon 10 (G>A) changes amino acids Arginine/Glutamine at codon 399. This polymorphism was reported to increase the risk of hepatocellular carcinoma in the Egyptian population (Surniyantoro et al, 2019;Naguib et al, 2020).…”