Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition

Gastroenterology. 2004 Apr;126(4):964-70. doi: 10.1053/j.gastro.2003.12.051.


Background & aims: Loss of genomic imprinting (LOI) of insulin-like growth factor II gene (IGF2) involves abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 has been associated with personal and family history of colorectal neoplasia (CRN), supporting a role for LOI in colorectal carcinogenesis. Whether LOI of IGF2 is associated with known environmental risk factors for CRN is unknown.

Methods: We performed quantitative hot-stop PCR for imprinting analysis of IGF2 on normal peripheral blood lymphocytes (PBL) of individuals. Environmental exposures including tobacco, alcohol, NSAIDs, and nutrient consumption (calcium, folate, selenium, fiber, and fat) were correlated with LOI expression in PBL. Odds ratios (OR) and 95% CI were calculated.

Results: The prevalence of LOI of IGF2 was examined in 172 individuals. Persons with CRN (adenomas/cancer) had 5.1-fold (95% CI: 1.92-13.6) increased risk of having LOI of IGF2 in PBL compared with those without CRN. In contrast, tobacco smoking (OR = 0.96, 95% CI: 0.36-2.55), alcohol consumption (OR = 1.22, 95% CI: 0.45-3.3), and NSAIDs use (OR = 1.21, 95% CI: 0.38-3.94) were not significantly associated with LOI of IGF2. Nutrient ingestion including calcium (P = 0.61), folate (P = 0.23), selenium (P = 0.19), fiber (P = 0.63), and fat (P = 0.14) was not statistically correlated with LOI of IGF2.

Conclusions: Abnormal imprinting of IGF2 gene was strongly associated with CRN but not with any of the environmental exposures examined. LOI of IGF2 does not appear to be an environmentally acquired phenomenon but rather a hereditary risk factor for CRN.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / epidemiology
  • Adenoma / genetics*
  • Aged
  • Alcohol Drinking / epidemiology
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Biomarkers
  • Calcium / administration & dosage
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / genetics*
  • Cross-Sectional Studies
  • Dietary Fats / administration & dosage
  • Dietary Fiber / administration & dosage
  • Environmental Exposure
  • Female
  • Folic Acid / administration & dosage
  • Genomic Imprinting*
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Risk Factors
  • Selenium / administration & dosage
  • Smoking / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Dietary Fats
  • Dietary Fiber
  • Insulin-Like Growth Factor II
  • Folic Acid
  • Selenium
  • Calcium