Association between XRCC1, ADPRT, hOGG1 and APE1 Polymorphisms and Cranial Nerve Palsy of Nasopharyngeal Carcinoma after Radiotherapy

• Main Authors: Wen-Ting Tzeng, 曾文廷
• Other Authors: Yi-Chih Chien
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/30388790141801766927

碩士 === 國立彰化師範大學 === 生物學系 === 99 === BACKGROUND: Several DNA repair gene polymorphisms have been described, which affect DNA repair capacity and the risk of cancer. We evaluated the association of six polymorphisms in the DNA base-excision repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ADPRT (Ala762Val), hOGG1 (Cys326Ser) and APE1 (Asp148Glu), with the risk of cranial nerve palsy following radiotherapy. BACKGROUND: Several DNA repair gene polymorphisms have been described, which affect DNA repair capacity and the risk of cancer. We evaluated the association of six polymorphisms in the DNA base-excision repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ADPRT (Ala762Val), hOGG1 (Cys326Ser) and APE1 (Asp148Glu), with the risk of cranial nerve palsy following radiotherapy. METHODS: We conducted this study in 69 nasopharyngeal carcinoma patients receiving radiotherapy; eighteen patients of them have cranial nerve palsy (CNP). Six common non-synonymous single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULT: After adjustment for sex and age, we found a reduced risk of developing CNP with the ADPRT 762Val allele in overall patients (OR = 0.20; 95% CI, 0.05–0.93). Compared with the major homozygote of XRCC1 codon194 or hOGG1 codon326 genotype, the risk for CNP was significantly decreased in individuals with the heterozygote genotype in male (OR = 0.18; 95% CI, 0.03–0.98 and OR = 0.18; 95% CI, 0.03–1.01, respectively). Further, the combined major homozygote of XRCC1 codon280 and hOGG1 codon326 was used as the reference, the findings indicated that a statistically significantly reduced risk of CNP was associated with the combined XRCC1-280 (Arg/Arg) and hOGG1-326 (Cys/Ser) (OR = 0.15; 95% CI, 0.03–0.73 and OR = 0.07; 95% CI, 0.01–0.71, respectively). Besides, in overall patients, we also found the risk of CNP was also reduced in the presence of the combined heterozygote of XRCC1 codon194 and ADPRT codon762 or the heterozygote of hOGG1 codon326 and ADPRT codon762 compared with major homozygote genotype in both gene groups, (OR = 0.06; 95% CI, 0.01–0.68 and OR = 0.05; 95% CI, 0.004–0.71, respectively). Most importantly, we significantly found heterozygote of XRCC1codon194 and hOGG1codon326 might affect the risk of CNP. Interestingly, in overall or male only, there was a significant difference in the median number of risk alleles between the CNP positive and the CNP negative groups (P = 0.027; P=0.048, respectively). CONCLUSION: The XRCC1 polymorphisms, especially the 194Trp allele, hOGG1 326Ser and ADPRT 762Val allele play an important role in radiation-related CNP development. These variants can interact together to further decrease susceptibility of radiation. Identifying these risk genetic markers could provide more insight into the side effects and may also provide information to develop better prevention and therapeutic strategies. Larger studies are needed to confirm our findings before these gene polymorphisms can be used as predictive markers to individualize radiotherapy on genetic bases.