Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition |
| |
Authors: | Cruz-Correa Marcia Cui Hengmi Giardiello Francis M Powe Neil R Hylind Linda Robinson Angela Hutcheon David F Kafonek David R Brandenburg Sheri Wu Yiqian He Xiaobing Feinberg Andrew P |
| |
Institution: | Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cruzm1@ccf.org |
| |
Abstract: | 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. |
| |
Keywords: | CRC colorectal cancer CRN colorectal neoplasia IGF2 insulin-like growth factor II gene LOI loss of imprinting PBL peripheral blood lymphocytes |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|