Siraj A K, Al-Rasheed M, Ibrahim M, Siddiqui K, Al-Dayel F, Al-Sanea O, Uddin S, Al-Kuraya K
Department of Human Cancer Genomics Research, Research Centre, KFNCCC & R, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
J Endocrinol Invest. 2008 Oct;31(10):893-9. doi: 10.1007/BF03346438.
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.
DNA修复基因的遗传多态性似乎决定了DNA修复能力。我们推测,负责DNA修复的基因多态性可能与甲状腺癌风险相关。为了评估DNA修复基因的遗传多态性在甲状腺癌中的作用,我们在沙特人群中开展了一项基于医院的病例对照研究。通过聚合酶链反应-限制性片段长度多态性分析了从沙特阿拉伯人群中招募的223例新发乳头状甲状腺癌病例和229例对照的8个选定DNA修复基因中的21个位点,包括非同源末端连接途径基因LIGIV(LIGlV ASP62HIS、PRO231SER、TRP46TER)、XRCC4剪接33243301G>A和XRCC7 ILE3434THR;同源重组途径基因XRCC3 ARG94HIS和THR241MET、RAD51非翻译区15452658T>C、15455419A>G、RAD52 2259和GLN221GLU、保守DNA损伤反应基因Tp53 PRO47SER、PRO72ARG、Tp53非翻译区7178189A>C以及碱基切除修复基因XRCC1 ARG194TRP、ARG280HIS、ARG399GLN、ARG559GLN。与野生型相比,RAD52 GLN221GLU基因型CG以及携带G等位基因的变体显示出统计学意义且患甲状腺癌的风险非常高[CG与CC相比;p<0.001,优势比(OR)=15.57,95%置信区间(CI)=6.56-36.98,CG+GG与CC相比;p<0.001,OR=17.58,95%CI=7.44-41.58]。同样,RAD52 2259基因型CT和变体等位基因T在风险评估方面存在显著差异(CT与CC相比;p<0.05,OR=1.53,95%CI=1.03-2.28,CT+TT与CC相比;p<0.001,OR=1.922,95%CI=1.31-2.82)。其余位点与风险无显著关联。在筛查的21个位点中,RAD52 2259和RAD52 GLN221GLU可能对疾病进程具有重要意义,并且可能与沙特阿拉伯人群的乳头状甲状腺癌风险相关。