Cancer Causes & Control

, Volume 26, Issue 3, pp 467–473 | Cite as

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization

  • Michael N. Passarelli
  • Polly A. Newcomb
  • Karen W. Makar
  • Andrea N. Burnett-Hartman
  • John D. Potter
  • Melissa P. Upton
  • Lee-Ching Zhu
  • Michael E. Rosenfeld
  • Stephen M. Schwartz
  • Carolyn M. Rutter
Original paper
First Online:
Received:
Accepted:

Abstract

Purpose

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.

Keywords

Cholesterol Colonoscopy Colorectal adenoma Colorectal hyperplastic polyp Mendelian randomization 
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Notes

Acknowledgments

We thank Joseph Webster (Group Health Research Institute), Jeanne DaGloria (Fred Hutchinson Cancer Research Center), Dr. Margaret Mandelson (Group Health Research Institute), and Dr. Santica Marcovina (University of Washington) for their contributions at various stages of this research. This work was supported by the National Cancer Institute at the National Institutes of Health (Grant Numbers R03CA171014, T32CA009168, K05CA152715, P01CA074184, R01CA097325). Pilot funding was provided by the Division of Public Health Sciences at Fred Hutchinson Cancer Research Center.

Conflict of interest

The authors declare no conflict of interests.

Supplementary material

10552_2015_526_MOESM1_ESM.pdf (133 kb)
Supplementary material 1 (PDF 132 kb)

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Michael N. Passarelli
    • 1
    • 2
  • Polly A. Newcomb
    • 1
    • 2
  • Karen W. Makar
    • 1
    • 2
  • Andrea N. Burnett-Hartman
    • 1
    • 2
  • John D. Potter
    • 1
    • 2
    • 3
  • Melissa P. Upton
    • 4
  • Lee-Ching Zhu
    • 5
  • Michael E. Rosenfeld
    • 4
    • 6
  • Stephen M. Schwartz
    • 1
    • 2
  • Carolyn M. Rutter
    • 5
    • 7
  1. 1.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of Epidemiology, School of Public HealthUniversity of WashingtonSeattleUSA
  3. 3.Centre for Public Health ResearchMassey UniversityWellingtonNew Zealand
  4. 4.Department of Pathology, School of MedicineUniversity of WashingtonSeattleUSA
  5. 5.Group Health Research InstituteSeattleUSA
  6. 6.Department of Environmental and Occupational Health Sciences, School of Public HealthUniversity of WashingtonSeattleUSA
  7. 7.Department of Biostatistics, School of Public HealthUniversity of WashingtonSeattleUSA

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