Research Papers:

CDH1 rs9929218 variant at 16q22.1 contributes to colorectal cancer susceptibility

Peng Han _, Guiyou Liu, Xin Lu, Minmin Cao, Youling Yan, Jing Zou, Xiaobo Li and Guangyu Wang

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Oncotarget. 2016; 7:47278-47286. https://doi.org/10.18632/oncotarget.9758

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Peng Han1, Guiyou Liu2, Xin Lu3, Minmin Cao4, Youling Yan3, Jing Zou5, Xiaobo Li6, Guangyu Wang7

1Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150040, China

2Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China

3Department of Gastroenterology, The First Hospital of Harbin, Harbin, 150001, China

4Department of Endocrinology, The First Hospital of Harbin, Harbin, 150001, China

5Department of Hematology, The First Hospital of Harbin, Harbin, 150001, China

6Department of Pathology, Harbin Medical University, Harbin, 150081, China

7Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150040, China

Correspondence to:

Xiaobo Li, email: [email protected]

Guangyu Wang, email: [email protected]

Keywords: genome-wide association study, colorectal cancer, rs9929218, meta-analysis, eQTL

Received: November 26, 2015    Accepted: May 08, 2016    Published: June 01, 2016


Colorectal cancer (CRC) is the third most common cancer. Large-scale genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants in European ancestry including the CDH1 rs9929218. Following GWAS and candidate studies evaluated the association between the CDH1 rs9929218 polymorphism and CRC in European, Asian and American populations. However, these studies reported inconsistent associations. Evidence shows that rs9929218 may regulate different gene expressions in different human tissues. Here, we reevaluated this association using large-scale samples from 16 studies (n=131768) using a meta-analysis method. In heterogeneity test, we did not identify significant heterogeneity among these studies. Meta-analysis using fixed effect model showed significant association between rs9929218 and CRC (P=6.16E-21, odds ratio (OR) =0.92, 95% confidence interval (CI) 0.91-0.94). In order to validate the effect of rs9929218 variant on CDH1 expression, we further performed a functional analysis using two large-scale expression datasets. We identified significant regulation relation between rs9929218 variant and the expression of CDH1, ZFP90, RP11-354M1.2 and MCOLN2 by both cis-effect and trans-effect. In summary, our analysis highlights significant association between rs9929218 polymorphism and CRC susceptibility.

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