title: Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.
abstract: OBJECTIVE
  Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation.
  
  
  METHODS
  We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health.
  
  
  RESULTS
  Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40 mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC increase: 0.99, 0.71-1.38).
  
  
  CONCLUSIONS
  Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA, 98109, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Passarelli
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Burnett-Hartman
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
authors.forename: Lee-Ching
authors.initials: LC
authors.lastname: Zhu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Rutter
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000209:etiology; D000328:Adult; D000368:Aged; D001706:Biopsy; D002784:Cholesterol / Q000097:blood*; D003111:Colonic Polyps / Q000097:blood* / Q000209:etiology* / Q000235:genetics; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000209:etiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*
chemical_list: D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol