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

被引:96
作者
Cruz-Correa, M
Cui, HM
Giardiello, FM
Powe, NR
Hylind, L
Robinson, A
Hutcheon, DF
Kafonek, DR
Brandenburg, S
Wu, YQ
He, XB
Feinberg, AP
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[2] Cleveland Clin, Dept Med, Weston, FL USA
[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[4] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[5] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD USA
关键词
D O I
10.1053/j.gastro.2003.12.051
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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: 1.9213.6) 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 = 121, 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 lGF2 gene was strongly associated with CRN but not with any of the environmental exposures examined. LOI of lGF2 does not appear to be an environmentally acquired phenomenon but rather a hereditary risk factor for CRN.
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页码:964 / 970
页数:7
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