Wang Jian-Xin, Yu Hua-Long, Bei Shao-Sheng, Cui Zhen-Hua, Li Zhi-Wen, Liu Zhen-Ji, Lv Yan-Feng
Department of Anoproctology, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
Med Sci Monit. 2016 Sep 26;22:3419-3425. doi: 10.12659/msm.896693.
BACKGROUND Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. More advanced work is required in the detection of biomarkers for CRC susceptibility and prognosis. High-mobility group box-1 (HMGB1) is an angiogenesis-related gene reported to be associated with the development of CRC. The direct evidence of HMGB1 gene polymorphisms as biomarkers for CRC has not been reported previously. MATERIAL AND METHODS A total of 240 CRC patients and 480 healthy controls were periodically enrolled. DNA was extracted from blood specimens. The distributions of SNPs of HMGB1 were determined by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS In this case-control study, we observed a significant association between overall CRC risk and SNP rs2249825 (CG vs. CC and GG vs. CC). Participants carrying both rs2249825 CG (OR, 2.67; 95% CI, 1.89 to 3.78) and rs2249825 GG genotypes (OR, 2.32; 95% CI, 1.13 to 4.73) had a significantly increased risk of developing CRC compared to those carrying GG genotype. rs2249825 was associated with the risk of CRC in the dominant model but not in the recessive model. However, we found no significant differences in the rs1412125 or rs1045411 polymorphisms in the HMGB1. Advanced analyses showed that the number of rs2249825 G alleles showed a significant relationship with risk of CRC. CONCLUSIONS Our results show an association between HMGB1 rs2249825 SNP and CRC incidence in the Chinese Han population. However, population-based studies with more subjects and prognostic effects are needed to verify the association of HMGB1 SNPs with CRC susceptibility, severity, and long-term prognosis.
结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。在结直肠癌易感性和预后生物标志物的检测方面,需要开展更深入的研究。高迁移率族蛋白B1(HMGB1)是一种与血管生成相关的基因,据报道与结直肠癌的发生有关。此前尚未有关于HMGB1基因多态性作为结直肠癌生物标志物的直接证据报道。
共纳入240例结直肠癌患者和480例健康对照者。从血液标本中提取DNA。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法确定HMGB1单核苷酸多态性(SNP)的分布情况。
在这项病例对照研究中,我们观察到总体结直肠癌风险与SNP rs2249825(CG与CC、GG与CC)之间存在显著关联。与携带GG基因型的参与者相比,同时携带rs2249825 CG基因型(比值比[OR],2.67;95%置信区间[CI],1.89至3.78)和rs2249825 GG基因型(OR,2.32;95% CI,1.13至4.73)的参与者患结直肠癌的风险显著增加。rs2249825在显性模型中与结直肠癌风险相关,但在隐性模型中不相关。然而,我们发现HMGB1基因的rs1412125或rs1045411多态性没有显著差异。进一步分析表明,rs2249825 G等位基因的数量与结直肠癌风险存在显著关系。
我们的研究结果表明,在中国汉族人群中,HMGB1 rs2249825 SNP与结直肠癌发病率之间存在关联。然而,需要更多受试者的基于人群的研究以及预后效应研究来验证HMGB1 SNPs与结直肠癌易感性、严重程度和长期预后之间的关联。