title: Meta association of colorectal cancer confirms risk alleles at 8q24 and 18q21.
abstract: BACKGROUND
  Genome-wide association studies of colorectal cancer (CRC) have identified genetic variants that reproducibly associate with CRC. Associations of 12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 (SMAD7) and CRC were investigated in a three-center collaborative study including two U.K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees.
  
  
  METHODS
  Our combined resource included 1,092 CRC case subjects and 1,060 age- and sex-matched controls. Meta statistics and Monte Carlo significance testing using Genie software provided a valid combined analysis of our mixed independent and related case-control resource. We also evaluated whether these associations differed by sex, age at diagnosis, family history, or tumor site.
  
  
  RESULTS
  At 8q24, we observed two independent significant associations at single nucleotide polymorphisms located in two different risk regions of 8q24: rs6983267 in region 3 [P(trend) = 0.01; per allele odds ratio (OR), 1.17; 95% confidence intervals (95% CI), 1.03-1.32] and rs10090154 in region 5 (P(trend) = 0.05; per allele OR, 1.24; 95% CI, 1.01-1.51). At 18q21, associations were observed in distal colon tumors but not in proximal or rectal cancers: rs4939827 (P(trend) = 0.007; per allele OR, 0.77; 95% CI, 0.64-0.93; case-case p(diff) = 0.03) and rs12953717 (P(trend) = 0.01; per allele OR, 1.27; 95% CI, 1.06-1.52). We were unable to detect any associations at 9p24 with CRC.
  
  
  CONCLUSIONS
  Our investigation confirms that variants across multiple risk regions of 8q24 are associated with CRC, and that associations at 18q21 differ by tumor site.
authors.affiliation: Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84109, USA. karen.curtin@hsc.utah.edu
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.forename: Rina
authors.initials: R
authors.lastname: George
authors.forename: Mark
authors.initials: M
authors.lastname: Katory
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shorto
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009010:Monte Carlo Method; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012984:Software; D006113:United Kingdom / Q000453:epidemiology; D014589:Utah / Q000453:epidemiology