Dataset Information

Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways.

ABSTRACT: We have compared DNA methylation in normal colon mucosa between patients with colon cancer and patients without cancer. We identified significant differences in methylation between the two groups at 114 to 874 genes. The majority of the differences are in pathways involved in the metabolism of carbohydrates, lipids, and amino acids. We also compared transcript levels of genes in the insulin signaling pathway. We found that the mucosa of patients with cancer had significantly higher transcript levels of several hormones regulating glucose metabolism and significantly lower transcript levels of a glycolytic enzyme and a key regulator of glucose and lipid homeostasis. These differences suggest that the normal colon mucosa of patients with cancer metabolizes dietary components differently than the colon mucosa of controls. Because the differences identified are present in morphologically normal tissue, they may be diagnostic of colon cancer and/or prognostic of colon cancer susceptibility.

SUBMITTER: Silviera ML

PROVIDER: S-EPMC3294197 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways.

Silviera Matthew L ML Smith Brian P BP Powell Jasmine J Sapienza Carmen C

Cancer prevention research (Philadelphia, Pa.) 20120201 3

We have compared DNA methylation in normal colon mucosa between patients with colon cancer and patients without cancer. We identified significant differences in methylation between the two groups at 114 to 874 genes. The majority of the differences are in pathways involved in the metabolism of carbohydrates, lipids, and amino acids. We also compared transcript levels of genes in the insulin signaling pathway. We found that the mucosa of patients with cancer had significantly higher transcript le ...[more]

PMID: 22300984

Similar Datasets

Project description:BACKGROUND:Chronological age is a prominent risk factor for many types of cancers including colorectal cancer (CRC). Yet, the risk of CRC varies substantially between individuals, even within the same age group, which may reflect heterogeneity in biological tissue aging between people. Epigenetic clocks based on DNA methylation are a useful measure of the biological aging process with the potential to serve as a biomarker of an individual's susceptibility to age-related diseases such as CRC. METHODS:We conducted a genome-wide DNA methylation study on samples of normal colon mucosa (N = 334). Subjects were assigned to three cancer risk groups (low, medium, and high) based on their personal adenoma or cancer history. Using previously established epigenetic clocks (Hannum, Horvath, PhenoAge, and EpiTOC), we estimated the biological age of each sample and assessed for epigenetic age acceleration in the samples by regressing the estimated biological age on the individual's chronological age. We compared the epigenetic age acceleration between different risk groups using a multivariate linear regression model with the adjustment for gender and cell-type fractions for each epigenetic clock. An epigenome-wide association study (EWAS) was performed to identify differential methylation changes associated with CRC risk. RESULTS:Each epigenetic clock was significantly correlated with the chronological age of the subjects, and the Horvath clock exhibited the strongest correlation in all risk groups (r > 0.8, p < 1 × 10-30). The PhenoAge clock (p = 0.0012) revealed epigenetic age deceleration in the high-risk group compared to the low-risk group. CONCLUSIONS:Among the four DNA methylation-based measures of biological age, the Horvath clock is the most accurate for estimating the chronological age of individuals. Individuals with a high risk for CRC have epigenetic age deceleration in their normal colons measured by the PhenoAge clock, which may reflect a dysfunctional epigenetic aging process.

Project description:Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development.Prevention relevanceOur study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.

Dataset Information

Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways.

Publications

Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets