Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer

Abstract

Background/Aims: In mammalian cells, XRCC3 plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to thyroid cancer. In this study, we used a haplotype-based approach to investigate whether 5 selected SNPs i.e. rs1799796, rs1799794, rs861539, rs709399 and rs861530 of XRCC3 gene are associated with thyroid cancer risk in 456 cancer patients and 400 cancer-free controls. Methods: Genotyping was performed using Allele-specific PCR followed by sequencing. Statistical analysis was performed to analyse gene and haplotype association. Results: After analysis, frequency of mutant genotype/alleles of SNPs (rs1799796, p<0.0001; rs1799794, p<0.0001; rs861539, p<0.001; rs709399, p <0.0001; rs861530, p<0.002) was found significantly higher in thyroid cancer patients compared to controls. Significant associations were found for most of the variant genotypes in SNPs of rs1799794, rs1799796, rs861539, rs861530 and rs709399 in papillary thyroid and follicular cancer patients compared to other histologic subtypes of thyroid carcinoma. Additionally, haplotype analysis revealed that haplotypes, AACGA (p= 0.0005), AGTAA (p= 0.008), GATAA (p= 0.001), GGCAA (p= 0.001) were linked with significant increase in thyroid cancer risk. However, haplotype AGCGG (p= 0.0009) was associated with a significant reduced thyroid cancer risk. Conclusion: Our results suggest that common genetic variants in the XRCC3 gene of DSBR pathway may modulate thyroid cancer risk.

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes

“…Indeed, prior studies by our team do suggest that SNPs across different DNA repair pathways – e.g., RAD51 and XRCC3 (HR pathway), CCNH (NER pathway) and MSH6 (MMR pathway) – may be implicated in TC (or, more specifically, DTC) predisposition [14,15,16,17,18]. Such studies add on to prior and subsequent work by other teams [8,12,19,20,21,22,23,24,25] that propose additional markers and reinforce the notion that DNA repair SNPs may contribute to DTC risk. However, besides being scarce, these studies provide only limited information on the impact of the studied SNP in specific subpopulations, e.g., male versus female patients or early-onset versus late-onset DTC.…”

“…Considering the specificities of DTC regarding gender distribution and median age at diagnosis [1,2] such detailed analysis could prove useful. Although gene-gene interactions could be of utmost importance in the real context, possibly decisive, they have only seldom evaluated and, when considered [19,20,22,24,26,27], analyses were usually limited to the combined effect of SNPs in the same gene or in genes of the same pathway. DNA repair proteins functionally interact with each other, both within the same DNA repair pathway and across different pathways, establishing ground for additive or even multiplicative effects of different SNPs (irrespective of their pathway) on DNA repair activity and, hence, cancer risk.…”

An IoT-Based Intelligent Wound Monitoring System

“…IoT based system used embedded sensing devices to efficiently and economically sense and record real time data [22,23,24]. We also used efficient sensors for real time data sensing.…”

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

“…The BRCA2 protein directly binds to and regulates the RAD51 protein, an essential molecule for DNA repair via homologous recombination (HR) (Fradet-Turcotte et al 2016, Katsuki & Takata 2016, Yan et al 2016, Sarwar et al 2017. BRCA2-deficient cancer cells are hypersensitive to DNA-crosslinking agents such as cisplatin (CDDP), and therefore BRCA2 may be a target for the management of platinum resistance (Sakai et al 2008, Rytelewski et al 2014, Katsuki & Takata 2016.…”