X线修复交错互补基因1-Arg399Gln多态性与宫颈癌急性放射性损伤的相关性

Correlation of XRCC1 Arg 399Gln polymorphism with acute irradiation injury of cervical cancer: report of 152 cases

目的探讨X线修复交错互补基因1（X-ray repair cross complementing group 1,XRCC1）-Arg399Gln多态性与宫颈癌急性放射性损伤的相关性。方法收集经病理活检证实为宫颈癌的患者152例。Sanger测序法检测外周血XRCC1基因单核苷酸多态性（single nucleotide polymorphism,SNP）,并分析其与急性放射性损伤致放射性膀胱炎和直肠炎发生的关系。结果 152例宫颈癌患者中,携带XRCC1 Arg/Arg、Arg/Gln、Gln/Gln基因型的分别有78、56、18例。其中发生2~3级急性膀胱炎有47例;2~3级急性直肠炎有100例,没有4级膀胱炎、直肠炎的发生。对其他临床因素校正后,多变量Logistic回归分析表明XRCC1 399密码子杂合变异基因型携带者（Arg/Gln）和纯合变异携带者（Gln/Gln）的2~3级膀胱炎发生风险显著高于野生型患者,分别为野生型的4.114倍（OR=4.114,95%CI：1.746~9.693）和9.096倍（OR=9.096,95%CI：2.707~30.566）;2~3级直肠炎发生风险分别是野生型的5.011倍（OR=5.011,95%CI：2.169~11.575）和7.165倍（OR=7.165,95%CI：1.506~34.092）。结论 XRCC1 399密码子的SNP与宫颈癌急性放射性膀胱炎和直肠炎有关,具有潜在的放射治疗副反应预测因子价值。

Objective To investigate the correlation of the polymorphism of X-ray repair cross complementing group 1（ XRCC1） Arg399 Gln with acute radiotherapy-induced injuries in cervical cancer.Methods A total of 152 patients with pathology-confirmed cervical cancer admitted in our hospital from July2011 to June 2015 were recruited in this study. Single nucleotide polymorphisms（ SNPS） in XRCC1 gene were analyzed by Sanger sequencing, and the results were evaluated with the occurrences of acute radiotherapy-induced cystitis and proctitis in the patients. Results In the cohort,there were 78,56 and 18 patients respectively carrying XRCC1 Arg / Arg,Arg / Gln,and Gln / Gln,and 47 cases of grade 2-3 acute cystitis,100 of grade 2-3 acute proctitis and none of grade 4 cystitis and proctitis. After adjustment for other clinical factors,multivariate logistic regression analysis indicated that the patients carrying XRCC1 399 Arg /Gln and 399 Gln / Gln had higher risk for the development of grade 2-3 cystitis when compared with those carrying wide type（ OR = 4. 114,95% CI： 1. 746 ~ 9. 693; OR = 9. 096; 95% CI： 2. 707 ~ 30. 566）,and were prone to having of grade 2-3 proctitis（ OR = 5. 011,95% CI： 2. 169 ~ 11. 575; OR = 7. 165; 95% CI：1. 506 ~ 34. 092）. Conclusion SNPs of XRCC1 codon 399 is related with acute radiotherapy-injured cystitis and proctitis in cervical cancer,and of potential predictive value for side effects of radiotherapy.