title: Systematic meta-analyses and field synopsis of genetic association studies in colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer is a major global public health problem, with approximately 950,000 patients newly diagnosed each year. We report the first comprehensive field synopsis and creation of a parallel publicly available and regularly updated database (CRCgene) that catalogs all genetic association studies on colorectal cancer (http://www.chs.med.ed.ac.uk/CRCgene/).
  
  
  METHODS
  We performed two independent systematic reviews, reviewing 10&emsp14;145 titles, then collated and extracted data from 635 publications reporting on 445 polymorphisms in 110 different genes. We carried out meta-analyses to derive summary effect estimates for 92 polymorphisms in 64 different genes. For assessing the credibility of associations, we applied the Venice criteria and the Bayesian False Discovery Probability (BFDP) test.
  
  
  RESULTS
  We consider 16 independent variants at 13 loci (MUTYH, MTHFR, SMAD7, and common variants tagging the loci 8q24, 8q23.3, 11q23.1, 14q22.2, 1q41, 20p12.3, 20q13.33, 3q26.2, 16q22.1, and 19q13.1) to have the most highly credible associations with colorectal cancer, with all variants except those in MUTYH and 19q13.1 reaching genome-wide statistical significance in at least one meta-analysis model. We identified less-credible (higher heterogeneity, lower statistical power, BFDP >0.2) associations with 23 more variants at 22 loci. The meta-analyses of a further 20 variants for which associations have previously been reported found no evidence to support these as true associations.
  
  
  CONCLUSIONS
  The CRCgene database provides the context for genetic association data to be interpreted appropriately and helps inform future research direction.
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, UK.
authors.forename: Evropi
authors.initials: E
authors.lastname: Theodoratou
authors.forename: Zahra
authors.initials: Z
authors.lastname: Montazeri
authors.forename: Steven
authors.initials: S
authors.lastname: Hawken
authors.forename: Genevieve CdL
authors.initials: GC
authors.lastname: Allum
authors.forename: Jacintha
authors.initials: J
authors.lastname: Gong
authors.forename: Valerie
authors.initials: V
authors.lastname: Tait
authors.forename: Iva
authors.initials: I
authors.lastname: Kirac
authors.forename: Mahmood
authors.initials: M
authors.lastname: Tazari
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.forename: Alex
authors.initials: A
authors.lastname: Demarsh
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: Denise
authors.initials: D
authors.lastname: Landry
authors.forename: Helen E
authors.initials: HE
authors.lastname: Benson
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Read
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Julian
authors.initials: J
authors.lastname: Little
mesh_terms: D001499:Bayes Theorem; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D003627:Data Interpretation, Statistical; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051906:Smad7 Protein / Q000235:genetics
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D045647:DNA Glycosylases; C061738:mutY adenine glycosylase