title: Insulin-like growth factor-II methylation status in lymphocyte DNA and colon cancer risk in the Northern Sweden Health and Disease cohort.
abstract: Loss of imprinting (LOI) of the insulin-like growth factor II (IGFII) gene is a frequent phenomenon in colorectal tumor tissues. Previous reports indicated that subjects with colorectal neoplasias show LOI of IGFII in circulating lymphocytes. Furthermore, LOI of IGFII is strongly related to the methylation of a differentially methylated region (DMR) in intron 2 of IGFII, suggesting that the methylation status could serve as a biomarker for early detection. Thus, hypermethylation of this DMR, even at a systemic level, e.g., in lymphocyte DNA, could be used for screening for colon cancer. To validate this, we performed a case-control study of 97 colon cancer cases and 190 age-matched and gender-matched controls, nested within the prospective Northern Sweden Health and Disease Study cohort. Methylation levels of the IGFII-DMR in lymphocyte DNA were measured at two specific CpG sites of the IGFII-DMR using a mass-spectrometric method called short oligonucleotide mass analysis, the measurements of which showed high reproducibility between replicate measurements for the two CpG sites combined and showed almost perfect validity when performed on variable mixtures of methylated and unmethylated standards. Mean fractions of CpG methylation, for the two CpG sites combined, were identical for cases and controls (0.47 and 0.46, respectively; P(difference) = 0.75), and logistic regression analyses showed no relationship between colon cancer risk and quartile levels of CpG methylation. The results from this study population do not support the hypothesis that colon cancer can be predicted from the different degrees of methylation of DMR in the IGFII gene from lymphocyte DNA.
authors: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. r.kaaks@dkfz.de
authors: Rudolf
authors: R
authors: Kaaks
authors: Pär
authors: P
authors: Stattin
authors: Stéphanie
authors: S
authors: Villar
authors: Anna R
authors: AR
authors: Poetsch
authors: Laure
authors: L
authors: Dossus
authors: Alexandra
authors: A
authors: Nieters
authors: Elio
authors: E
authors: Riboli
authors: Richard
authors: R
authors: Palmqvist
authors: Göran
authors: G
authors: Hallmans
authors: Christoph
authors: C
authors: Plass
authors: Marlin D
authors: MD
authors: Friesen
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005602:France / Q000453:epidemiology; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism*; D007438:Introns / Q000235:genetics; D008214:Lymphocytes / Q000502:physiology*; D008745:Methylation; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology
chemical_list: D007335:Insulin-Like Growth Factor II