Xiangyu Ma1, Ben Zhang, Wei Zheng. 1. Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, , Chongqing, China.
Abstract
OBJECTIVE: In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies. DESIGN: We searched PubMed and Google Scholar to identify papers that investigated associations between genetic variants and CRC risk and published through 25 December 2012. With data from 950 papers, we conducted 910 meta-analyses for 267 genetic variants in 150 candidate genes with at least three data sources. We used Venice criteria and false-positive report probability tests to grade levels of cumulative epidemiological evidence of significant associations with CRC risk. RESULTS: Sixty-two variants in 50 candidate genes showed a nominally significant association with CRC risk (p<0.05). Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLH1 and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes. Additionally, 40 variants in 33 genes showed convincing evidence of no association with CRC risk in meta-analyses including at least 5000 cases and 5000 controls. CONCLUSIONS: Approximately 4% of genetic variants evaluated to date in candidate-gene association studies showed moderate to strong cumulative epidemiological evidence of an association with CRC risk. These genetic variants, if confirmed, may explain approximately 5% of familial CRC risk.
OBJECTIVE: In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies. DESIGN: We searched PubMed and Google Scholar to identify papers that investigated associations between genetic variants and CRC risk and published through 25 December 2012. With data from 950 papers, we conducted 910 meta-analyses for 267 genetic variants in 150 candidate genes with at least three data sources. We used Venice criteria and false-positive report probability tests to grade levels of cumulative epidemiological evidence of significant associations with CRC risk. RESULTS: Sixty-two variants in 50 candidate genes showed a nominally significant association with CRC risk (p<0.05). Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLH1 and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes. Additionally, 40 variants in 33 genes showed convincing evidence of no association with CRC risk in meta-analyses including at least 5000 cases and 5000 controls. CONCLUSIONS: Approximately 4% of genetic variants evaluated to date in candidate-gene association studies showed moderate to strong cumulative epidemiological evidence of an association with CRC risk. These genetic variants, if confirmed, may explain approximately 5% of familial CRC risk.
Authors: M G F van Lier; A Wagner; E M H Mathus-Vliegen; E J Kuipers; E W Steyerberg; M E van Leerdam Journal: Am J Gastroenterol Date: 2010-01-05 Impact factor: 10.864
Authors: Brent W Zanke; Celia M T Greenwood; Jagadish Rangrej; Rafal Kustra; Albert Tenesa; Susan M Farrington; James Prendergast; Sylviane Olschwang; Theodore Chiang; Edgar Crowdy; Vincent Ferretti; Philippe Laflamme; Saravanan Sundararajan; Stéphanie Roumy; Jean-François Olivier; Frédérick Robidoux; Robert Sladek; Alexandre Montpetit; Peter Campbell; Stephane Bezieau; Anne Marie O'Shea; George Zogopoulos; Michelle Cotterchio; Polly Newcomb; John McLaughlin; Ban Younghusband; Roger Green; Jane Green; Mary E M Porteous; Harry Campbell; Helene Blanche; Mourad Sahbatou; Emmanuel Tubacher; Catherine Bonaiti-Pellié; Bruno Buecher; Elio Riboli; Sebastien Kury; Stephen J Chanock; John Potter; Gilles Thomas; Steven Gallinger; Thomas J Hudson; Malcolm G Dunlop Journal: Nat Genet Date: 2007-07-08 Impact factor: 38.330
Authors: Christina M Lill; Johannes T Roehr; Matthew B McQueen; Fotini K Kavvoura; Sachin Bagade; Brit-Maren M Schjeide; Leif M Schjeide; Esther Meissner; Ute Zauft; Nicole C Allen; Tian Liu; Marcel Schilling; Kari J Anderson; Gary Beecham; Daniela Berg; Joanna M Biernacka; Alexis Brice; Anita L DeStefano; Chuong B Do; Nicholas Eriksson; Stewart A Factor; Matthew J Farrer; Tatiana Foroud; Thomas Gasser; Taye Hamza; John A Hardy; Peter Heutink; Erin M Hill-Burns; Christine Klein; Jeanne C Latourelle; Demetrius M Maraganore; Eden R Martin; Maria Martinez; Richard H Myers; Michael A Nalls; Nathan Pankratz; Haydeh Payami; Wataru Satake; William K Scott; Manu Sharma; Andrew B Singleton; Kari Stefansson; Tatsushi Toda; Joyce Y Tung; Jeffery Vance; Nick W Wood; Cyrus P Zabetian; Peter Young; Rudolph E Tanzi; Muin J Khoury; Frauke Zipp; Hans Lehrach; John P A Ioannidis; Lars Bertram Journal: PLoS Genet Date: 2012-03-15 Impact factor: 5.917
Authors: Hannah Maynard; Zsofia K Stadler; Michael F Berger; David B Solit; Michele Ly; Maeve A Lowery; Diana Mandelker; Liying Zhang; Emmett Jordan; Imane El Dika; Yelena Kemel; Marc Ladanyi; Mark E Robson; Eileen M O'Reilly; Ghassan K Abou-Alfa Journal: Cancer Date: 2020-02-03 Impact factor: 6.860
Authors: Jolantha Beyerle; Andreana N Holowatyj; Mariam Haffa; Eva Frei; Biljana Gigic; Petra Schrotz-King; Juergen Boehm; Nina Habermann; Marie Stiborova; Dominique Scherer; Torsten Kölsch; Stephanie Skender; Nikolaus Becker; Esther Herpel; Martin Schneider; Alexis Ulrich; Peter Schirmacher; Jenny Chang-Claude; Hermann Brenner; Michael Hoffmeister; Ulrike Haug; Robert W Owen; Cornelia M Ulrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-11-18 Impact factor: 4.254