BACKGROUND: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. METHODS: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. RESULTS: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)). CONCLUSIONS: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. IMPACT: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.
BACKGROUND:Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. METHODS: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. RESULTS: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)). CONCLUSIONS: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. IMPACT: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.
Authors: Albert Tenesa; Susan M Farrington; James G D Prendergast; Mary E Porteous; Marion Walker; Naila Haq; Rebecca A Barnetson; Evropi Theodoratou; Roseanne Cetnarskyj; Nicola Cartwright; Colin Semple; Andrew J Clark; Fiona J L Reid; Lorna A Smith; Kostas Kavoussanakis; Thibaud Koessler; Paul D P Pharoah; Stephan Buch; Clemens Schafmayer; Jürgen Tepel; Stefan Schreiber; Henry Völzke; Carsten O Schmidt; Jochen Hampe; Jenny Chang-Claude; Michael Hoffmeister; Hermann Brenner; Stefan Wilkening; Federico Canzian; Gabriel Capella; Victor Moreno; Ian J Deary; John M Starr; Ian P M Tomlinson; Zoe Kemp; Kimberley Howarth; Luis Carvajal-Carmona; Emily Webb; Peter Broderick; Jayaram Vijayakrishnan; Richard S Houlston; Gad Rennert; Dennis Ballinger; Laura Rozek; Stephen B Gruber; Koichi Matsuda; Tomohide Kidokoro; Yusuke Nakamura; Brent W Zanke; Celia M T Greenwood; Jagadish Rangrej; Rafal Kustra; Alexandre Montpetit; Thomas J Hudson; Steven Gallinger; Harry Campbell; Malcolm G Dunlop Journal: Nat Genet Date: 2008-03-30 Impact factor: 38.330
Authors: Sari Tuupanen; Mikko Turunen; Rainer Lehtonen; Outi Hallikas; Sakari Vanharanta; Teemu Kivioja; Mikael Björklund; Gonghong Wei; Jian Yan; Iina Niittymäki; Jukka-Pekka Mecklin; Heikki Järvinen; Ari Ristimäki; Mariachiara Di-Bernardo; Phil East; Luis Carvajal-Carmona; Richard S Houlston; Ian Tomlinson; Kimmo Palin; Esko Ukkonen; Auli Karhu; Jussi Taipale; Lauri A Aaltonen Journal: Nat Genet Date: 2009-06-28 Impact factor: 38.330
Authors: Mark M Pomerantz; Nasim Ahmadiyeh; Li Jia; Paula Herman; Michael P Verzi; Harshavardhan Doddapaneni; Christine A Beckwith; Jennifer A Chan; Adam Hills; Matt Davis; Keluo Yao; Sarah M Kehoe; Heinz-Josef Lenz; Christopher A Haiman; Chunli Yan; Brian E Henderson; Baruch Frenkel; Jordi Barretina; Adam Bass; Josep Tabernero; José Baselga; Meredith M Regan; J Robert Manak; Ramesh Shivdasani; Gerhard A Coetzee; Matthew L Freedman Journal: Nat Genet Date: 2009-06-28 Impact factor: 38.330
Authors: Rosalind A Eeles; Zsofia Kote-Jarai; Graham G Giles; Ali Amin Al Olama; Michelle Guy; Sarah K Jugurnauth; Shani Mulholland; Daniel A Leongamornlert; Stephen M Edwards; Jonathan Morrison; Helen I Field; Melissa C Southey; Gianluca Severi; Jenny L Donovan; Freddie C Hamdy; David P Dearnaley; Kenneth R Muir; Charmaine Smith; Melisa Bagnato; Audrey T Ardern-Jones; Amanda L Hall; Lynne T O'Brien; Beatrice N Gehr-Swain; Rosemary A Wilkinson; Angie Cox; Sarah Lewis; Paul M Brown; Sameer G Jhavar; Malgorzata Tymrakiewicz; Artitaya Lophatananon; Sarah L Bryant; Alan Horwich; Robert A Huddart; Vincent S Khoo; Christopher C Parker; Christopher J Woodhouse; Alan Thompson; Tim Christmas; Chris Ogden; Cyril Fisher; Charles Jamieson; Colin S Cooper; Dallas R English; John L Hopper; David E Neal; Douglas F Easton Journal: Nat Genet Date: 2008-02-10 Impact factor: 38.330
Authors: Ji Luo; Michael J Emanuele; Danan Li; Chad J Creighton; Michael R Schlabach; Thomas F Westbrook; Kwok-Kin Wong; Stephen J Elledge Journal: Cell Date: 2009-05-29 Impact factor: 41.582
Authors: Michael N Passarelli; Polly A Newcomb; Karen W Makar; Andrea N Burnett-Hartman; John D Potter; Melissa P Upton; Lee-Ching Zhu; Michael E Rosenfeld; Stephen M Schwartz; Carolyn M Rutter Journal: Cancer Causes Control Date: 2015-01-25 Impact factor: 2.506