Increased Risk of Differentiated Thyroid Carcinoma with Combined Effects of Homologous Recombination Repair Gene Polymorphisms in an Iranian Population (original) (raw)
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Haplotype analysis of XRCC1 gene polymorphisms and the risk of thyroid carcinoma
Purpose: Variants in DNA repair genes may alter the repair mechanisms that make the persons vulnerable to DNA damage. These polymorphic variants in the DNA repair pathway genes, such as XRCC1, have been associated with susceptibility of several types of cancer including thyroid cancer. This study was designed to explore the link between XRCC1 polymorphisms and modulation of thyroid cancer risk. Methods: Our study consisted of 456 thyroid cancer patients and 400 controls. For XRCC1 polymorphisms analyses, three single nucleotide polymorphisms (SNPs) (rs25489, rs25487 and 1799782) were selected and genotyped by ARMS-PCR. Results: The homozygous mutant (AA) of rs25489 SNP showed highly significant association with thyroid cancer risk (OR=0.17; 95%CI=0.10-0.31; p=0.0001). In the rs25487 polymorphism all genotypes showed no significantly increased risk of thyroid cancer in patients compared to controls (p>0.05). In the rs1799782 of XRCC1 gene, the homozygous mutant (TT) significantly decreased the risk of thyroid cancer (OR=0.71; 95%CI=0.50-1.01; p=0.05). Eight haplotypes were generated for three selected SNPs (rs25489, rs25487 and rs1799782) of XRCC1 gene among thyroid cases and controls. The haplotype GAT (OR=1.69; p=0.0005) and GGC (OR=2.75; showed highly significant association with increased risk of thyroid cancer. The haplotypes AAC (OR=0.31;, AAT (OR= 0.51; p=0.001), AGT (OR=0.46; p=0.0003) and GGT (OR=0.80; p=0.03) had significant reducing effect in thyroid cancer patients.
Genetics and Molecular Biology, 2012
Homologous recombination (HR) is the major pathway for repairing double strand breaks (DSBs) in eukaryotes and XRCC2 is an essential component of the HR repair machinery. To evaluate the potential role of mutations in gene repair by HR in individuals susceptible to differentiated thyroid carcinoma (DTC) we used high resolution melting (HRM) analysis, a recently introduced method for detecting mutations, to examine the entire XRCC2 coding region in an Iranian population. HRM analysis was used to screen for mutations in three XRCC2 coding regions in 50 patients and 50 controls. There was no variation in the HRM curves obtained from the analysis of exons 1 and 2 in the case and control groups. In exon 3, an Arg 188 His polymorphism (rs3218536) was detected as a new melting curve group (OR: 1.46; 95%CI: 0.432-4.969; p = 0.38) compared with the normal melting curve. We also found a new Ser 150 Arg polymorphism in exon 3 of the control group. These findings suggest that genetic variations in the XRCC2 coding region have no potential effects on susceptibility to DTC. However, further studies with larger populations are required to confirm this conclusion.
Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2017
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. Genotyping was performed using Allele-specific PCR followed by sequencing. Statistical analysis was performed to analyse gene and haplotype association. 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 ...
International Journal of Cancer Management, 2017
Background: The thyroid cancer (TC) is one of endocrine malignancies which contributes to more than 50% of all deaths from endocrine cancers. Gene polymorphisms including DNA repair genes such as XRCC1 (X-ray repair cross-complementing group 1) gene are thought to modify DNA repair capacity and relate to cancer risk. Objectives: The aim of the study was to detect the association between XRCC1 polymorphisms and increased risk of thyroid carcinoma among Iranian-Azeri patients. Methods: This case-control study was performed on 114 differentiated thyroid carcinoma patients and 91 normal control subjects. Single nucleotide polymorphisms (SNPs) of 194 C > T and 399 G > A of XRCC1 gene were genotyped by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP). Results: In the present study, polymorphism at codon 194 of the XRCC1 gene was not found in case and control groups (P = NC (not calculated). All of the case and control subjects were 194C/C. Unlike 399 G > A genotype (P < 0.001, OR = 0.184, CI = 0.09-0.372), there was a positive association for 399G/G (P < 0.001, OR = 3.304, CI = 1.624-6.780) and 399 A/A (P < 0.001, OR = 14.143, CI = 1.861-296.277) genotypes with differentiated thyroid carcinoma. The frequency of variant 399 A allele among the cases was slightly higher than that in controls (P = 0.269, OR = 0.798, CI = 0.535-1.190). Conclusions: Based on these results, the XRCC1 399 G > A genotype could be used as a useful molecular biomarker to predict genetic susceptibility for differentiated thyroid carcinoma in Iranian-Azeri patients.
Balkan Journal of Medical Genetics, 2021
Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto’s thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain p...
Association of Polymorphisms in ERCC2 Gene with Non-Familial Thyroid Cancer Risk
Cancer Epidemiology, Biomarkers & Prevention, 2005
The ERCC2 protein is an evolutionary conserved ATPdependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp ! Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys ! Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid-type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid-type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results.
Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk
Scientific Reports, 2015
A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR 5 1.36, 95%CI 1.20-1.53, p-value 5 7.41 3 10 27 ) and rs1203952 (FOXA2, OR 5 1.29, 95%CI 1.16-1.44, p-value 5 4.42 3 10 26 ). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend 5 3.13 3 10 247 ). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.
Association of Polymorphisms in ERCC2 Gene with Non-Familial Thyroid Cancer Risk
Cancer Epidemiology Biomarkers & Prevention, 2005
The ERCC2 protein is an evolutionary conserved ATPdependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp ! Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys ! Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid -type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid -type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results. (Cancer Epidemiol Biomarkers Prev
Asian Pacific journal of cancer prevention : APJCP, 2017
Background: A number of case-control studies have evaluated associations between the X-ray cross complementary group 1 protein (XRCC1) gene rs1799782 (Arg194Trp), rs25487 (Arg399Gln) and rs25489 (Arg280His) polymorphisms and thyroid cancer (TC) risk, but the results remain inconclusive. Materials and Methods: A systematic literature search was performed using PubMed and Google Scholar Search. According to defined criteria data were extracted and pooled odds ratios with 95% confidence intervals were calculated under five genetic models. Results: A total of 8 studies with 1,672 cases and 2,805 controls for the rs1799782 polymorphism, 14 studies with 2,506 cases and 5,180 controls for the rs25487 polymorphism, and 11 studies with 2,197 cases and 4,761 controls for the rs25489 polymorphism were included in this meta-analysis. Overall, there was a statistical association between XRCC1 rs1799782 polymorphism and TC risk with the homozygote genetic model (TT vs. CC: OR = 1.815, 95% CI = 1....