Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women.

Loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that is polymorphic in the population, and its presence may predispose an individual to the development of colorectal cancer. We evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. Among 40 participants, 11 (27.5%) had LOI of IGF-II in their normal colonic mucosal tissue. After adjusting for body mass index and family history of colorectal cancer, LOI status was associated with a fivefold increased risk of adenoma formation (odds ratio = 5.2, 95% confidence interval = 1.0 to 26.7). On average, IGF-II expression was more than threefold higher among women with LOI of IGF-II than among women with normal imprinting status. Our findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer. These findings are intriguing and need to be confirmed in larger studies.

[1]  A. Feinberg,et al.  Loss of IGF2 Imprinting: A Potential Marker of Colorectal Cancer Risk , 2003, Science.

[2]  A. Feinberg,et al.  Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. , 2002, Cancer research.

[3]  A. Feinberg,et al.  Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. , 2001, Journal of the National Cancer Institute.

[4]  M. Surani,et al.  Imprinting and the Epigenetic Asymmetry Between Parental Genomes , 2001, Science.

[5]  M. Oshimura,et al.  Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma , 2001, Molecular carcinogenesis.

[6]  B. Tycko,et al.  Epigenetic heterogeneity at imprinted loci in normal populations. , 2001, Biochemical and biophysical research communications.

[7]  C. Plass,et al.  Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  W. Reik,et al.  Genomic imprinting: parental influence on the genome , 2001, Nature Reviews Genetics.

[9]  K. Pfeifer,et al.  Mechanisms of genomic imprinting. , 2000, American journal of human genetics.

[10]  G. Yang,et al.  Molecular alterations of p73 in human esophageal squamous cell carcinomas: loss of heterozygosity occurs frequently; loss of imprinting and elevation of p73 expression may be related to defective p53. , 2000, Carcinogenesis.

[11]  E. Xing,et al.  Molecular alterations of p 73 in human esophageal squamous cell carcinomas : loss of heterozygosity occurs frequently ; loss of imprinting and elevation of p 73 expression may be related to defective p 53 , 2000 .

[12]  N. Miller,et al.  Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. , 1999, Cancer research.

[13]  B. Tycko.  Genomic imprinting and cancer. , 1999, Results and problems in cell differentiation.

[14]  A. Feinberg,et al.  Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability , 1998, Nature Medicine.

[15]  T. Vu,et al.  Increased Expression of the Insulin-like Growth Factor-II Gene in Wilms' Tumor Is Not Dependent on Loss of Genomic Imprinting or Loss of Heterozygosity* , 1996, The Journal of Biological Chemistry.