长链非编码RNA H19变异基因型与中国人群肾细胞癌发病风险及预后的相关性研究
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国家自然科学基金(81772111);南京市卫生科技发展专项(YKK19146)


Association study of genetic variant in long non⁃coding RNA H19 and renal cell carcinoma susceptibility and prognosis in Chinese population
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    摘要:

    目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)H19的rs2839698、rs217727、rs3741216和rs3741219这4个位点的多态性遗传变异对肾细胞癌(renal cell carcinoma,RCC)易感性和预后的影响。方法:本研究为自2004年5月开始的两阶段病例对照研究,共纳入1 014例RCC患者及1 063例健康对照者。其中第一阶段298例RCC患者具有完整的随访资料。采用TaqMan探针法实时聚合酶链反应检测患者外周血的4个位点多态性基因分型,通过计算比值比(odds ratio,OR)和95%置信区间(confidence interval,CI)评估H19多态性与RCC发生风险及临床特征的关系;Kaplan-Meier曲线评估临床特征与H19 4个位点不同基因型的生存状态,采用COX回归分析计算不同基因型、TNM分期及病理分级发生死亡结局的风险比(hazardratio,HR)和95%CI,评估影响RCC预后的独立危险因素。结果:与H19的rs2839698 CC基因型相比,CT/TT基因型人群患RCC风险增加(P=0.012,OR=1.13,95%CI=1.02~1.55)。CT/TT基因型患者更容易发生大体积肿瘤(P=0.003,OR=1.35,95%CI=1.10~1.73)和临床高分期(P=0.010,OR=1.63,95%CI=1.08~2.21);rs2839698 CT/TT基因型RCC患者的5年总生存率明显低于CC基因型RCC患者(CT/TT vs. CC:Log-rank P=0.027,HR=2.24,95%CI=1.10~4.59)。结论:H19 rs2839698位点基因变异同RCC易感性和生存相关,其具体的功能影响仍需进一步研究验证。

    Abstract:

    Objective:This study aims to clarify the effects of H19 genetic variant rs2839698,rs217727,rs3741216 and rs3741219 on renal cell carcinoma(RCC) susceptibility and prognosis. Methods:We conducted this two-stage case-control study with a total of 1 014 RCC cases and 1 063 controls since May 2004. Total 298 RCC cases in the first stage had complete follow-up data available. Genotyping was performed using TaqMan real-time polymerase chain reaction assays. Odds ratio(OR)and 95% confidence interval(CI) were calculated to evaluate the association between H19 polymorphism and RCC risk and clinical characteristics. Kaplan-Meier method was utilized to assess the survival of H19 polymorphisms. Hazard ratio(HR)and 95%CI were calculated by COX regression model to discover whether genotypes,TNM and grade were the independent prognostic factors. Results:Compared with the H19 rs2839698 CC genotype,the variant genotypes(CT/TT)were significantly associated with increased risk of RCC(P=0.012,OR=1.13,95% CI=1.02-1.55). Besides,patients with variant genotypes(CT/TT)were more likely to develop large tumor(P=0.003,OR=1.35,95% CI=1.10-1.73)and advanced disease(P=0.010,OR=1.63,95% CI=1.08-2.21);and had a significantly unfavorable 5-year survival than those with the rs2839698 CC genotype(CT/TT vs. CC:Log-rank P=0.027,HR=2.24,95%CI=1.10-4.59). Conclusion:The results suggested that H19 rs2839698 variant may be a genetic predictor of susceptibility and mortality of RCC. The precise functional impact of the variant on H19 still needs further experimental validation.

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邓夏珩,吕 强,李鹏超.长链非编码RNA H19变异基因型与中国人群肾细胞癌发病风险及预后的相关性研究[J].南京医科大学学报(自然科学版),2021,(11):1607-1613

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  • 收稿日期:2021-07-07
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  • 在线发布日期: 2021-12-13
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