title: Common genetic variant on BMP4 contributes to colorectal adenoma and cancer: A meta-analysis based on 15 studies.
abstract: Epidemiological studies indicate a genetic contribution to colorectal cancer (CRC), but specific genetic variants remain unknown. Genome-wide association studies have identified rs4444235 at BMP4 as a new colorectal cancer (CRC) and colorectal adenoma (CRA) susceptibility locus in populations of European descent. After that, several validation studies have been conducted among various ethnic populations to investigate if the SNP was associated with CRC/CRA, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis involving 54,631 CRC cases, 3995 CRA cases and 88,098 controls from 15 studies was performed. Potential sources of heterogeneity including ethnicity, sample size, study design and endpoint were also assessed. Overall, the summary OR of CRC was 1.06 (95% CI: 1.04-1.08, P<10(-5)). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians (OR=1.07, 95% CI: 1.01-1.12, P=0.01) and Caucasians (OR=1.07, 95% CI: 1.05-1.10, P<10(-5)); while no significant associations were found among African Americans and other ethnic populations in all genetic models. In addition, significant associations were also detected for CRA with per-allele OR of 1.09 (95% CI: 1.03-1.14, P=0.001). Our findings demonstrated that BMP4-rs4444235 is a risk factor associated with increased CRC and CRA susceptibility, but these associations vary in different ethnic populations.
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Lei
authors: L
authors: Zhou
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Jun
authors: J
authors: Xie
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Er-li
authors: EL
authors: Gu
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Yao
authors: Y
authors: Huang
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Yan
authors: Y
authors: Qu
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Ai-Ping
authors: AP
authors: Xu
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China.
authors: Yin
authors: Y
authors: Zhu
authors: Department of Gastroenterology, Jing'an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing'an Branch), 200040, PR China. Electronic address: hong_wang001@126.com.
authors: Hong
authors: H
authors: Wang
mesh_terms: D000236:Adenoma / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D063369:Knowledge Discovery; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4
keywords: 14q22.2–rs4444235; BMP4; Colorectal adenoma; Colorectal cancer; Meta-analysis