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Functional polymorphisms of the lncRNA H19 promoter region contribute to the cancer risk and clinical outcomes in advanced colorectal cancer

文献类型：期刊论文

作者Qin, Wenyan2; Wang, Xiaodong2; Wang, Yilin2; Li, Yalun3; Chen, Qiuchen2; Hu, Xiaoyun2; Wu, Zhikun2; Zhao, Pengfei2; Li, Shanqiong2; Zhao, Haishan2
刊名CANCER CELL INTERNATIONAL
出版日期2019-08-20
卷号19期号:1页码:12
关键词H19 Genetic polymorphisms Susceptibility Colorectal cancer Prognosis
DOI10.1186/s12935-019-0895-x
通讯作者Ding, Jian(jding@simm.ac.cn) ; Wei, Minjie(mjwei@cmu.edu.cn) ; Wu, Huizhe(wuhz@cmu.edu.cn)
英文摘要Background The long non-coding RNA H19 plays critical roles in cancer occurrence, development, and progression. The present study is for the first time to evaluate the association of genetic variations in the H19 promoter region with advanced colorectal cancer (CRC) susceptibility, environmental factors, and clinical outcomes. Methods 16 single-nucleotide polymorphisms (SNPs) were identified in the H19 gene promoter by DNA sequencing, and 3 SNPs among which including rs4930101, rs11042170, and rs2735970 further expanded samples with 572 advanced CRC patients and 555 healthy controls. Results We found that harboring SNP [rs4930101 (P = 0.009), rs2735970 (P = 0.003), and rs11042170 (P = 0.003)] or carrying more than one combined risk genotypes significantly increased the risk for CRC [P < 0.0001, adjusted OR (95% CI) 6.48 (2.97-14.15)]. In the correlation analysis with environmental factors, rs2735970 and gender, combined risk genotypes (> 1 vs. <= 1) and family history of cancer demonstrated significant interactions. Furthermore, a remarkably worse clinical outcome was found in combined risk genotypes (> 1 vs. <= 1), especially in CRC patients with body weight >= 61 kg, smoking, and first-degree family history of cancer (Log-rank test: P = 0.006, P = 0.018, and P = 0.013, respectively). More importantly, the multivariate Cox regression analyses further verified that combined risk genotypes > 1 showed a prognostic risk factor for CRC patients with body weight >= 61 kg (P = 0.002), smoking (P = 0.008), and family history of cancer (P = 0.006). In addition, MDR analysis consistently revealed that the combination of selected SNPs and nine known risk factors showed a better prediction prognosis and represented the best model to predict advanced CRC prognosis. Conclusion 3 SNPs of rs4930101, rs11042170, and rs27359703 among 16 identified SNPs of H19 gene remarkably increased CRC risk. Furthermore, the combined risk genotypes had a significant impact on environmental factors and clinical outcomes in the advanced CRC patients with body weight >= 61 kg, ever-smoking, and first-degree family history of cancer. These data suggest that H19 promoter SNPs, especially these combined SNPs might be more potentially functional biomarkers in the prediction of advanced CRC risk and prognosis.
WOS关键词NONCODING RNA H19 ; CHRONIC INFLAMMATION ; PERIPHERAL-BLOOD ; GENE-EXPRESSION ; LUNG-CANCER ; CELL-GROWTH ; SUSCEPTIBILITY ; CLASSIFICATION ; IDENTIFICATION ; ASSOCIATION
资助项目National Natural Science Foundation of China[31828005] ; National Natural Science Foundation of China[81872905] ; National Natural Science Foundation of China[81673475] ; National Natural Science Foundation of China[81501346] ; National Natural Science Foundation of China[81603149] ; National Natural Science Foundation of China[81601370] ; National Natural Science Foundation of China[U1608281] ; Shenyang ST Projects[17-123-9-00] ; Shenyang ST Projects[Z18-4-020] ; Key Laboratory Foundation from Shenyang ST Projects[F16-094-1-00] ; Key Laboratory Foundation from Liaoning Province[LS201617] ; Liaoning Provincial Department of Education Scientific Research Project[LK201646] ; National Natural Science Foundation of Liaoning[U1608281]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000482761600001
出版者BMC
源URL[http://119.78.100.183/handle/2S10ELR8/288621]  
专题新药研究国家重点实验室
通讯作者Ding, Jian; Wei, Minjie; Wu, Huizhe
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
2.China Med Univ, Liaoning Key Lab Mol Targeted Antitumor Drug Dev, Sch Pharm, Dept Pharmacol, Shenyang 110122, Liaoning, Peoples R China
3.China Med Univ, Hosp 1, Dept Anorectal Surg, Shenyang 110001, Liaoning, Peoples R China
推荐引用方式
GB/T 7714		 Qin, Wenyan,Wang, Xiaodong,Wang, Yilin,et al. Functional polymorphisms of the lncRNA H19 promoter region contribute to the cancer risk and clinical outcomes in advanced colorectal cancer[J]. CANCER CELL INTERNATIONAL,2019,19(1):12.
APA Qin, Wenyan.,Wang, Xiaodong.,Wang, Yilin.,Li, Yalun.,Chen, Qiuchen.,...&Wu, Huizhe.(2019).Functional polymorphisms of the lncRNA H19 promoter region contribute to the cancer risk and clinical outcomes in advanced colorectal cancer.CANCER CELL INTERNATIONAL,19(1),12.
MLA Qin, Wenyan,et al."Functional polymorphisms of the lncRNA H19 promoter region contribute to the cancer risk and clinical outcomes in advanced colorectal cancer".CANCER CELL INTERNATIONAL 19.1(2019):12.

入库方式： OAI收割

来源：上海药物研究所

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