Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition.
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.
Cruz-Correa
Marcia
M
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cruzm1@ccf.org
Cui
Hengmi
H
Giardiello
Francis M
FM
Powe
Neil R
NR
Hylind
Linda
L
Robinson
Angela
A
Hutcheon
David F
DF
Kafonek
David R
DR
Brandenburg
Sheri
S
Wu
Yiqian
Y
He
Xiaobing
X
Feinberg
Andrew P
AP
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
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