Xu Xiao-Ling, Zheng Ji, Mao Wei-Min, Ling Zhi-Qiang
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou, 310022, China.
Key laboratory on Diagnosis and Treatment Technology on Thoracic Cancer, Hangzhou, Zhejiang, 310022, China.
Cancer Med. 2016 Aug;5(8):2084-90. doi: 10.1002/cam4.703. Epub 2016 Jun 23.
Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine-based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age- and sex-matched population controls using SNaPshot detection technology. Logistic regression, odds ratios (OR), and 95% confidence intervals were calculated to estimate lung cancer risk associated with SNP genotypes and haplotypes, after adjusting for case-control matching factors. Compared with the T/T and A/T genotype of RRM1 *151A>T, the A/A genotype had an increased risk for overall lung cancer (adjusted OR, 1.33). Additionally, the T/T+T/C genotypes of RRM1 -756T>C were risk factors that increased the susceptibility to lung cancer (adjusted OR 1.54, as compared with the C/C genotype). While the T/T+G/T genotypes of RRM1 -585T>G behaved as protective factors to increase the susceptibility to lung cancer (adjusted OR 0.44, as compared with the C/C genotype). In summary, this is the first study to systematically identify the relationship between the polymorphisms of RRM1 and individual susceptibility to lung cancer. It is anticipated that the RRM1 *151A>T, RRM1 -756T>C, and RRM1 -585T>G polymorphisms will improve the predictive prognosis of lung cancer sensitivity.
核糖核苷酸还原酶M1（RRM1）是DNA修复中的关键基因。最近的研究表明，RRM1表达可能是接受包括肺癌在内的基于吉西他滨辅助化疗的癌症患者生存或化疗敏感性的有力预测指标。然而，RRM1的单核苷酸多态性（SNP）与肺癌化疗易感性之间的关系尚未得到充分研究。我们使用SNaPshot检测技术在1007例原发性肺癌患者和1007例年龄及性别匹配的人群对照中检测了RRM1基因型的6个标签SNP。在调整病例对照匹配因素后，计算逻辑回归、比值比（OR）和95%置信区间，以估计与SNP基因型和单倍型相关的肺癌风险。与RRM1 *151A>T的T/T和A/T基因型相比，A/A基因型的总体肺癌风险增加（调整后OR为1.33）。此外，RRM1 -756T>C的T/T+T/C基因型是增加肺癌易感性的危险因素（与C/C基因型相比，调整后OR为1.54）。而RRM1 -585T>G的T/T+G/T基因型是增加肺癌易感性的保护因素（与C/C基因型相比，调整后OR为0.44）。总之，这是第一项系统鉴定RRM1多态性与个体肺癌易感性之间关系的研究。预计RRM1 *151A>T、RRM1 -756T>C和RRM1 -585T>G多态性将改善肺癌敏感性的预测预后。
