Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas.

Autor:	Montazeri Z; School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada., Theodoratou E; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., Nyiraneza C; School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada., Timofeeva M; Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK., Chen W; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., Svinti V; Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK., Sivakumaran S; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., Gresham G; School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada., Cubitt L; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., Carvajal-Carmona L; Biochemistry and Molecular Medicine, Genome and Biomedical Sciences Facility, UC Davis School of Medicine, University of California Davis, Davis, CA, USA., Bertagnolli MM; Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA., Zauber AG; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and., Tomlinson I; Wellcome Trust Centre for Human Genetics, Oxford, UK., Farrington SM; Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK., Dunlop MG; Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK., Campbell H; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK, Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital, Edinburgh, UK., Little J; School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada, jlittle@uottawa.ca.
Jazyk:	angličtina
Zdroj:	International journal of epidemiology [Int J Epidemiol] 2016 Feb; Vol. 45 (1), pp. 186-205. Date of Electronic Publication: 2015 Oct 07.
DOI:	10.1093/ije/dyv185
Abstrakt:	Background: Low penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/]. Methods: We performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations. Results: We considered the association with the rs6983267 variant at 8q24 as 'highly credible', reaching genome-wide statistical significance in at least one meta-analysis model. We identified 'less credible' associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations. Conclusions: The limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRA gene database provides context for CRA genetic association data and will help inform future research directions. (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu