Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk
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ABSTRACT:
PROVIDER: PRJNA549184 | ENA |
REPOSITORIES: ENA
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Project description:Genome wide DNA methylation profiling of normal colon samples. The Illumina Infinium HumanMethylation450 and EPIC Beadchip arrays were used to obtain DNA methylation profiles across approximately 450,000 and 850,000 CpGs. Samples were from nomal colons of 334 subjects with low, medium or high CRC risk according to their personal adenoma or cancer history.
2019-12-31 | GSE132804 | GEO
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.
| S-EPMC6942339 | biostudies-literature
Project description:To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers' putatively targeted genes, we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function Two biological replicates of HCT116 were compared to the data of two normal colon samples already deposited in GEO (GSM1010974 and GSM1010942).
2014-10-01 | E-GEOD-52429 | biostudies-arrayexpress
Project description:Atlas of the aging mouse colon
| PRJNA707433 | ENA
Project description:Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis
| PRJNA777445 | ENA
Project description:Colon cancer is one of the leading causes of death within the western world and is linked to the aging of the colon. The disease presents differently between men and women, developing in different parts of the colon and often with a different morphology. The colonic epithelium is a rapidly renewing tissue, tasked with absorption of water and nutrients, interacting with a wide array of intestinal microbes. The gut-associated lymphoid tissue houses the majority of all immune cells. These immune cells interact with and help regulate the activity of epithelial cells. However, not much is known whether compartment-specific changes occur during aging and how said changes could impact the epithelium. Here we show that both epithelial and immune cells differ significantly between colonic compartments and experience age-related changes, with the possible causal interactions. We found a shift in the absorptive-secretory cell balance, the decrease in colonocytes possibly linked to age-associated malabsorption and intestinal disturbances. We demonstrate marked changes in the aging of the immune cells with regard to populations and interactions with epithelial cells, linking aged immune cell produced cytokines (Ifn-γ, Il1B) and the aging of colonic epithelium, which lines up with observations of inflammation causing or exacerbating age-associated gut disfunctions, such as colon cancer. Our results provide new insights into the normal and age-associated states of the colon. We anticipate our work will provide a foundation for further inquiry not only into diseases of the colon (even outside the realm of aging research) but developmental research as well.
2022-03-31 | GSE168448 | GEO
Project description:To understand the funtion of Colorectal cancer GWAS results, we perform a comprehensive analysis using biofeatures of HCT116 colon cancer cell line and got a list of risk-asscociated SNP. Risk-associated SNP are likely exerting their effects through promoters or enhancer. In order to understand the importance of the genes with risk-associated SNP in their promoters and enhancers' putatively targeted genes, we did a comparison of these genes between HCT116 colon cancer cell and normal colon and try to understand their function
2014-10-01 | GSE52429 | GEO
Project description:IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2
| PRJNA750059 | ENA
Project description:To investigate whether lifestyle factors modulate the stability of gene promoter methylation in the normal aging colonic mucosa, we performed genome-scale DNA methylation profiling of 178 normal colon biopsies using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified Aspirin use and hormonal replacement therapy (HRT) suppress, whereas a high body mass index (BMI) and smoking promote age-related hyermethylation. Many of these loci modulated by lifestyle in the healthy colon mucosa coincide with loci hypermethylated in colorectal cancers and down-regulated in adenomas. The data show that lifestyle modulates the stability of DNA methylation in the aging colonic epithelium and thereby impacts the rate of evolution of cancer methylomes. Bisulphite converted DNA from the 178 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2014-07-01 | E-GEOD-48988 | biostudies-arrayexpress
Project description:To investigate whether lifestyle factors modulate the stability of gene promoter methylation in the normal aging colonic mucosa, we performed genome-scale DNA methylation profiling of 178 normal colon biopsies using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified Aspirin use and hormonal replacement therapy (HRT) suppress, whereas a high body mass index (BMI) and smoking promote age-related hyermethylation. Many of these loci modulated by lifestyle in the healthy colon mucosa coincide with loci hypermethylated in colorectal cancers and down-regulated in adenomas. The data show that lifestyle modulates the stability of DNA methylation in the aging colonic epithelium and thereby impacts the rate of evolution of cancer methylomes.
2014-07-01 | GSE48988 | GEO