title: A comparison of approaches for association studies of polymorphisms and colorectal cancer risk.
abstract: OBJECTIVE
  Meta-analyses have been used to evaluate associations between polymorphisms and colorectal cancer risk, but the quality of individual studies used to inform them may vary substantially. Our aim was to apply well-established quality-control criteria to individual association studies and then compare the results of meta-analyses that included or excluded studies that did not meet these criteria.
  
  
  METHODS
  We used meta-analyses of studies reporting a relationship between polymorphisms and colorectal cancer published between 1996 and 2008. Polymorphism-cancer associations were derived in separate meta-analyses including only those meeting the quality-control criteria.
  
  
  RESULTS
  Relative ORs varied substantially between the open and restricted group meta-analyses for all variants except MTHFR 677 CT. However, the associations were modest and the direction of relative risk did not change after applying criteria. Publication bias was detected for all associations, except the restricted set of studies for GSTP1 GG.
  
  
  CONCLUSIONS
  We observed variation in calculated relative risk and changes in tests for publication bias that were dependent on the inclusion criteria used for association studies of polymorphisms and colorectal cancer. Standardizing study inclusion criteria may reduce the variation in findings for meta-analyses of gene-association studies of common diseases such as colorectal cancer.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. sramsey@fhcrc.org
authors.forename: S D
authors.initials: SD
authors.lastname: Ramsey
authors.forename: R S
authors.initials: RS
authors.lastname: Holmes
authors.forename: C L
authors.initials: CL
authors.lastname: McDermott
authors.forename: D K
authors.initials: DK
authors.lastname: Blough
authors.forename: K L
authors.initials: KL
authors.lastname: Petrin
authors.forename: E M
authors.initials: EM
authors.lastname: Poole
authors.forename: C M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D015201:Meta-Analysis as Topic; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017594:Publication Bias; D012307:Risk Factors
chemical_list: D001191:Arylamine N-Acetyltransferase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C573423:MTHFR protein, human; C089384:N-acetyltransferase 1; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human