title: Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cruzm1@ccf.org
authors.forename: Marcia
authors.initials: M
authors.lastname: Cruz-Correa
authors.forename: Hengmi
authors.initials: H
authors.lastname: Cui
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: Neil R
authors.initials: NR
authors.lastname: Powe
authors.forename: Linda
authors.initials: L
authors.lastname: Hylind
authors.forename: Angela
authors.initials: A
authors.lastname: Robinson
authors.forename: David F
authors.initials: DF
authors.lastname: Hutcheon
authors.forename: David R
authors.initials: DR
authors.lastname: Kafonek
authors.forename: Sheri
authors.initials: S
authors.lastname: Brandenburg
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: He
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D015415:Biomarkers; D002118:Calcium / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004043:Dietary Fiber / Q000008:administration & dosage; D004781:Environmental Exposure; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012643:Selenium / Q000008:administration & dosage; D012907:Smoking / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D004041:Dietary Fats; D004043:Dietary Fiber; D007335:Insulin-Like Growth Factor II; D005492:Folic Acid; D012643:Selenium; D002118:Calcium