RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population

Abstract

Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity. We hypothesized that polymorphisms of genes responsible for DNA repair may be associated with risk of thyroid cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in thyroid cancer, we conducted a hospital-based case-control study in Saudi population. Two hundred and twenty-three incident papillary thyroid cancer cases and 229 controls recruited from Saudi Arabian population were analyzed for 21 loci in 8 selected DNA repair genes by PCR-restriction fragment length polymorphism including non-homologous end joining pathway genes LIGIV (LIGlV ASP62HIS, PRO231SER, TRP46TER), XRCC4 Splice 33243301G>A and XRCC7 ILE3434THR; homologous recombination pathway genes XRCC3 ARG94HIS and THR241MET, RAD51 UTR 15452658T>C, 15455419A>G, RAD52 2259 and GLN221GLU, conserved DNA damage response gene Tp53 PRO47SER, PRO72ARG, Tp53 UTR 7178189A>C and base excision repair gene XRCC1 ARG194TRP, ARG280HIS, ARG399GLN, ARG559GLN. RAD52 GLN221GLU genotypes CG and variants carrying G allele showed statistical significance and very high risk of developing thyroid cancer compared to wild type [CG vs CC; p<0.001, odds ratio (OR)=15.57, 95% confidence interval (CI)=6.56-36.98, CG+GG vs CC; p<0.001, OR=17.58, 95% CI=7.44-41.58]. Similarly, RAD52 2259 genotypes CT and variant allele T showed a significant difference in terms of risk estimation (CT vs CC; p<0.05, OR=1.53, 95% CI=1.03-2.28, CT+TT vs CC; p<0.001, OR=1.922, 95% CI=1.31-2.82). Remaining loci demonstrated no significance with risk. Of the 21 loci screened, RAD52 2259 and RAD52 GLN221GLU may be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population.

X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

“…However, the results were not consistent. For example, Ryu's study (Ryu et al, 2011) have found that the XRCC1 Arg194Trp Arg/ Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype (OR with 95 CI;), however, no such association was observed in Esfahani's study (Fard-Esfahani et al, 2011); Quispes's study (García-Quispes et al, 2011) have found a positive association (OR = 1.58, 95% CI 1.05-2.46) for XRCC1 Arg280His, however, no such tendency was found in Chiang's study (Chiang et al, 2008); Akulevich's study (Akulevich et al, 2009) have found that XRCC1 Arg399Gln polymorphisms was associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance, however, Siraj's study (Siraj et al, 2008) found no such association. These inconsistent results failed to clarify the complicated relationship between XRCC1 polymorphism and thyroid cancer risk.…”

“…There are also some case-control studies conducted to explore the association of SNPs of XRCC1 and thyroid cancer risk (Zhu et al, 2004;Chiang et al, 2008;Siraj et al, 2008;Akulevich et al, 2009;Ho et al, 2009;Sigurdson et al, 2009;Fard-Esfahani et al, 2011;García-Quispes et al, 2011;Ryu et al, 2011). However, the results were not consistent.…”

Associations Between XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms and Risk of Differentiated Thyroid Carcinoma: A Meta-analysis

“…Figure 1 illustrates the study selection process and the detailed characteristics of the included studies are shown in Table 1. A total of 10 published studies (1,606 DTC patients and 3,577 controls) were included in the Arg399Gln analysis (Zhu et al, 2004;Siraj et al, 2008;Chiang et al, 2008;Ho et al, 2009;Akulevich et al, 2009;Sigurdson et al, 2009;Ryu et al, 2011;Garcia-Quispes et al, 2011;Fard-Esfahani et al, 2011;Santos et al, 2012) Santos et al, 2012). The genotypic distribution of the controls was consistent with HWE, with the exception of two studies (Sigurdson et al, 2009;Ryu et al, 2011).…”

“…Three of these included Asian populations (Zhu et al, 2004;Chiang et al, 2008;Ryu et al, 2011), and two included a Caucasian population (Fard-Esfahani et al, 2011;Santos et al, 2012). Six relevant studies with a total number of 1,284 cases and 2,265 controls were included in the Arg280His analysis (Siraj et al, 2008;Chiang et al, 2008;Ho et al, 2009;Akulevich et al, 2009;FardEsfahani et al, 2011;Garcia-Quispes et al, 2011); one of these was based on Asian populations (Chiang et al, 2008), and four on Caucasian populations (Siraj et al, 2008;Akulevich et al, 2009;Fard-Esfahani et al, 2011;Garcia-Quispes et al,2011).…”

Increased Risk of Differentiated Thyroid Carcinoma with Combined Effects of Homologous Recombination Repair Gene Polymorphisms in an Iranian Population

“…Likewise, other studies in the Portuguese (Bastos et al, 2009) and Spanish population (Garcia-Quispes et al, 2011) did not reveal an association of XRCC2 R188H and thyroid cancer risk. In the Saudi Arabian population however, Rad52 2259C>T was associated with papillary thyroid cancer risk (Siraj et al, 2008).…”