International Journal of Colorectal Disease

, Volume 27, Issue 12, pp 1587–1595 | Cite as

Genetic variation in insulin pathway genes and distal colorectal adenoma risk

  • A. Joan LevineEmail author
  • Ugonna Ihenacho
  • Won Lee
  • Jane C. Figueiredo
  • David J. Vandenberg
  • Christopher K. Edlund
  • Brian D. Davis
  • Mariana C. Stern
  • Robert W. Haile
Original Article



Insulin, glucose, and other insulin-related proteins that mediate insulin signaling are associated with colorectal neoplasia risk, but associations with common genetic variation in insulin axis genes are less clear. In this study, we used a comprehensive tag single-nucleotide polymorphisms (SNPs) approach to define genetic variation in six insulin axis genes (IGF1, IGF2, IGFBP1, IGFBP3, IRS1, and IRS2) and three genes associated with estrogen signaling (ESR1, ESR2, and PGR).


We assessed associations between SNPs and distal colorectal adenoma (CRA) risk in a case–control study of 1,351 subjects. Cases were individuals with one or more adenomas diagnosed during sigmoidoscopy, and controls were individuals with no adenomas at the sigmoidoscopy exam. We used unconditional logistic regression assuming an additive model to assess SNP-specific risks adjusting for multiple comparisons with P act.


Distal adenoma risk was significantly increased for one SNP in IGF2 [per minor allele OR = 1.41; 95 % confidence interval (CI) = 1.16, 1.67; P act = 0.005] and decreased for an ESR2 SNP (per minor allele OR = 0.78; 95 % CI = 0.66, 0.91; P act = 0.041). There was no statistically significant heterogeneity of these associations by race, sex, BMI, physical activity, or, in women, hormone replacement therapy use. Risk estimates did not differ in the colon versus rectum or for smaller (<1 cm) versus larger (>1 cm) adenomas.


These data suggest that selected genetic variability in IGF2 and ESR2 may be modifiers of CRA risk.


Colorectal adenoma Tag SNP Insulin axis Estrogen receptors 



We would like to thank all the subjects who contributed their time to this study. We would also like to thank Terry Kolb and Jessie Lin for their assistance with data collection, cleaning and management and Anh Diep and for her assistance with biospecimen management. This work was supported by the National Cancer Institute, National Institutes of Health under 1R01 CA096830 and 5P01 CA42710.

Potential conflicts of interest

No authors report any conflict of interest. The content of the manuscript does not necessarily reflect the views or policies of the National Cancer Institute nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Supplementary material

384_2012_1505_MOESM1_ESM.xlsx (267 kb)
Supplementary Table 1 Genotype effects by race (XLSX 267 kb)
384_2012_1505_MOESM2_ESM.xlsx (105 kb)
Supplementary Table 2 Genotype effects by sex (XLSX 104 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Joan Levine
    • 1
    Email author
  • Ugonna Ihenacho
    • 1
  • Won Lee
    • 1
  • Jane C. Figueiredo
    • 1
  • David J. Vandenberg
    • 1
  • Christopher K. Edlund
    • 1
  • Brian D. Davis
    • 1
  • Mariana C. Stern
    • 1
  • Robert W. Haile
    • 1
  1. 1.Department of Preventive Medicine, Genetic EpidemiologyUniversity of Southern California Keck School of MedicineLos AngelesUSA

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