HMGB1相关基因多态性对中国汉族乳腺癌患者无病生存期和总生存期的影响

目的研究中国汉族女性乳腺癌患者高迁移率族蛋白B1(high mobility group box 1,HMGB1)相关基因遗传变异与无病生存期(DFS)和总生存期(OS)之间的关系。方法回顾性分析2010年5月~2015年10月期间我院收治的420例乳腺癌患者的临床资料,分析8个基因的166个单核苷酸多态性(SNPs),并采用多变量Cox比例风险模型来估计SNPs的风险比和95%置信区间(CI),在多基因风险评分的累积水平评估SNPs对乳腺癌预后的影响。结果与DFS显著相关的SNPs是MMP2基因的单核苷酸多态性,分别为rs243867位点(HR为1.28,95%CI为1.02~1.52,P0.05)和rs243842位点(HR为1.25,95%CI为1.04~1.55,P0.05)。而与OS相关的SNPs为MMP2基因的rs243842位点(HR为1.35,95%CI=1.01~1.74,P0.05)、HMGB1基因的rs4145277位点(HR为1.31,95%CI=1.01~1.68,P0.05)、TLR2基因的rs7656411位点(HR为0.78,95%CI,0.58~0.99,P0.05)和TLR4基因的rs7045953位点(HR为0.51,95%CI=0.27~0.88,P0.05)。DFS和OS患者的多基因风险评分结果显示,其第三个三分位数风险比率分别为1.79(95%CI=1.29~2.41)和2.84(95%CI=1.84~4.51)。结论 HMGB1相关基因的遗传多态性与乳腺癌患者的预后有关。

Effects of HMGB1-related gene polymorphisms on disease-free survival and overall survival in Chinese Han patients with breast cancer

Objective To study the relationship between genetic variation of high mobility group box 1(HMGB1)-related genes and disease free survival(DFS)and total survival(OS)in Chinese Han women with breast cancer.Methods The clinical data of 420 patients with breast cancer who were admitted to our hospital from May 2010 to October 2015 were retrospectively analyzed.166 single nucleotide polymorphisms(SNPs)of 8 genes were analyzed,and the multivariate Cox proportional hazards model was used to estimate the risk ratio of SNPs and 95%confidence interval(CI).The effect of SNPs on the prognosis of breast cancer was assessed at the cumulative level of polygenic risk score.Results SNPs significantly associated with DFS were single nucleotide polymorphisms of the MMP2 gene,which were locus rs243867(HR 1.28,95%CI 1.02-1.52,P<0.05)and locus rs243842(HR 1.25,95%CI 1.04-1.55,P<0.05).SNPs associated with OS were locus rs243842 of the MMP2 gene(HR=1.35,95%CI=1.01-1.74,P<0.05),locus rs 4145277 of HMGB1 gene(HR=1.31,95%CI=1.01-1.68,P<0.05),locus rs7656411 of TLR2 gene(HR 0.78,95%CI 0.58-0.99,P<0.05)and locus rs7045953 of the TLR4 gene(HR 0.51,95%CI=0.27-0.88,P<0.05).The results of polygenic risk score for DFS and OS patients showed a third tertile risk ratio was 1.79(95%CI=1.29-2.41)and 2.84(95%CI=1.84-4.51).Conclusion The genetic polymorphism of HMGB1-related gene is related to the prognosis of breast cancer patients.