Intronic polymorphisms in genes LRFN2 (rs2494938) and DNAH11 (rs2285947) are prognostic indicators of esophageal squamous cell carcinoma
Intronic polymorphisms in genes LRFN2 (rs2494938) and DNAH11 (rs2285947) are prognostic indicators of esophageal squamous cell carcinoma
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基因LRFN2（rs2494938）和DNAH11（rs2285947）的内含子多态性是食管鳞状细胞癌的预后指标
DOI：
10.1186/s12881-019-0796-9
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发表时间：
2019-05
影响因子：
--
通讯作者：
Chen Xiaofei
中科院分区：
文献类型：
--
作者：
Wang Jiru;Wang Qiuzi;Wei Bin;Zhou Yu;Qian Zhaoye;Gao Yong;Chen Xiaofei
背景：全基因组关联研究（GWAS）已成为筛查与疾病风险和预后相关的遗传变异的主要手段。最近的GWAS发现了三个新的内含子单核苷酸多态性基因LRFN 2（rs 2494938），DNAH 11（rs 2285947）和PLCXD 2（rs 2399395）与食管鳞状细胞癌（ESCC）的风险改变在中国汉族人群中。然而，这些变化在ESCC的预后意义仍然不清楚。方法：调查三个新的单核苷酸多态性（rs 2494938，rs 2285947，rs 2399395）与ESCC患者的预后的关联，我们招募了287例ESCC患者手术切除治疗，并通过Kaplan-Meier生存分析，对数秩检验和考克斯比例风险回归模型评估这三个多态性的潜在意义。结果：ESCC患者携带基因型AA在rs 2494938有较差的生存和基因型GG在2285947有较好的预后（对数秩P = 0.003和对数秩P = 0.037，分别）。此外，6p21.1处的rs 2494938与隐性模型中ESCC患者的总生存期独立相关[AA vs. GG/GA，HR = 3.12，95%CI = 1.43-6.83，P = 0.004]，7p15.3处的rs 2285947与显性模型中ESCC患者的总生存期独立相关[AA/GA vs. GG，HR = 1.59，95% CI = 1.02-2.49，P = 0.042]和累加模型[AA vs. GA vs. GG，HR = 1.45，95% CI = 1.05-2.01，P = 0.025]。本研究表明，6p21.1的rs 2494938和7p15.3的rs 2285947多态性可能是食管鳞癌独立的预后生物标志物，提示其相关基因LRFN 2和DNAH 11在食管鳞癌发生发展过程中可能具有生物学作用。
Background:Genome wide association study (GWAS) has become the major means to screen for the genetic variants associated with risk and prognosis of different diseases. A recent GWAS has discovered three novel intronic single nucleotide polymorphisms in genes LRFN2 (rs2494938), DNAH11 (rs2285947) and PLCXD2 (rs2399395) that are associated with altered risk of esophageal squamous cell carcinoma (ESCC) among Han Chinese populations. However, the prognostic significance of these variations in ESCC remains unclear.Methods:To investigate the association of three novel single nucleotide polymorphisms (rs2494938, rs2285947, rs2399395) with the prognosis of ESCC patients, we recruited 287 ESCC patients treated with surgical resection and evaluated the potential significance of the three polymorphisms through Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards regression models.Results:The ESCC patients carrying genotype AA at rs2494938 had worse survival and genotype GG at 2285947 had better prognosis (Log-rank P = 0.003 and Log-rank P = 0.037, respectively). In addition, rs2494938 at 6p21.1 was independently associated with overall survival of ESCC patients in recessive model [AA vs. GG/GA, HR = 3.12, 95% CI = 1.43-6.83, P = 0.004], rs2285947 at 7p15.3 was independently associated with overall survival of ESCC patients in both dominant model [AA/GA vs. GG, HR = 1.59, 95% CI = 1.02-2.49, P = 0.042] and additive model [AA vs. GA vs. GG, HR = 1.45, 95% CI = 1.05-2.01, P = 0.025].Conclusions:This study demonstrated that the polymorphisms rs2494938 at 6p21.1 and rs2285947 at 7p15.3 may serve as independent prognostic biomarkers for ESCC, implying the potential biological role of their related genes (LRFN2 and DNAH11) in the process of ESCC development.
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DOI：
10.2147/cpaa.s90367
发表时间：
2015
期刊：
Clinical pharmacology : advances and applications
影响因子：
--
作者：
North WG;Liu F;Tian R;Abbasi H;Akerman B
通讯作者：
Akerman B
影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
5.3
作者：
Wang, CY;Chang, K;Wenthold, RJ
通讯作者：
Wenthold, RJ
影响因子：
6.4
作者：
Liu, Jun-Wei;Kim, Myoung Sook;Sidransky, David
通讯作者：
Sidransky, David
来自全基因组关联研究的 6p21.1 上的遗传变异 rs10484761 与中国人群的胃癌生存相关
影响因子：
3.5
作者：
Kang, Meiyun;Ding, Ojie;Zhang, Zhengdong
通讯作者：
Zhang, Zhengdong