Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research

Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.

[1]  A. Maugeri,et al.  Adherence to the Mediterranean diet partially mediates socioeconomic differences in leukocyte LINE-1 methylation: evidence from a cross-sectional study in Italian women , 2020, Scientific Reports.

[2]  F. Basile,et al.  The Liquid Biopsy in the Management of Colorectal Cancer: An Overview , 2020, Biomedicines.

[3]  P. A. van den Brandt,et al.  Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis. , 2020, The American journal of gastroenterology.

[4]  A. Maugeri,et al.  The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer , 2020, Updates in Surgery.

[5]  P. Buckhaults,et al.  Early-onset colorectal cancer: initial clues and current views , 2020, Nature Reviews Gastroenterology & Hepatology.

[6]  Sean K. Maden,et al.  Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk , 2020, Clinical Epigenetics.

[7]  A. Goel,et al.  Epigenetics of colorectal cancer: biomarker and therapeutic potential , 2020, Nature Reviews Gastroenterology & Hepatology.

[8]  S. Hägg,et al.  Should we invest in biological age predictors to treat colorectal cancer in the older adults? , 2019, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[9]  Li Li,et al.  Association of Epigenetic Clock with Consensus Molecular Subtypes and Overall Survival of Colorectal Cancer , 2019, Cancer Epidemiology, Biomarkers & Prevention.

[10]  A. Maugeri,et al.  Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies , 2019, International journal of molecular sciences.

[11]  A. Maugeri,et al.  Dietary Patterns are Associated with Leukocyte LINE-1 Methylation in Women: A Cross-Sectional Study in Southern Italy , 2019, Nutrients.

[12]  N. Pavlidis,et al.  The Developing Story of Predictive Biomarkers in Colorectal Cancer , 2019, Journal of personalized medicine.

[13]  Genevieve L. Stein-O’Brien,et al.  Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and BrafV600E-Induced Tumorigenesis. , 2019, Cancer cell.

[14]  F. Basile,et al.  Biomarkers in colorectal cancer: Current clinical utility and future perspectives , 2018, World journal of clinical cases.

[15]  A. Maugeri,et al.  Mediterranean Diet and Particulate Matter Exposure Are Associated With LINE-1 Methylation: Results From a Cross-Sectional Study in Women , 2018, Front. Genet..

[16]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[17]  M. Libra,et al.  Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development , 2018, Aging.

[18]  D. English,et al.  DNA methylation‐based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies , 2018, International journal of cancer.

[19]  Steve Horvath,et al.  DNA methylation-based biomarkers and the epigenetic clock theory of ageing , 2018, Nature Reviews Genetics.

[20]  M. Levine,et al.  An epigenetic biomarker of aging for lifespan and healthspan , 2018, bioRxiv.

[21]  C. Gong,et al.  MicroRNAs and cancer: Key paradigms in molecular therapy. , 2017, Oncology letters.

[22]  J. R. Tejedor,et al.  Distinct chromatin signatures of DNA hypomethylation in aging and cancer , 2017, bioRxiv.

[23]  R. Marioni,et al.  Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins , 2017, bioRxiv.

[24]  H. Arkenau,et al.  Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade , 2017, BioMed research international.

[25]  J. Murabito,et al.  Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits , 2017, Aging cell.

[26]  B. Kim,et al.  Measurement of biological age may help to assess the risk of colorectal adenoma in screening colonoscopy , 2017, World journal of gastroenterology.

[27]  A. Maugeri,et al.  LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia , 2017, BMC Cancer.

[28]  Chuanhua Yang,et al.  Prognostic Value of microRNA-224 in Various Cancers: A Meta-analysis. , 2017, Archives of medical research.

[29]  Nancy L. Pedersen,et al.  Biological Age Predictors , 2017, EBioMedicine.

[30]  Xueli Zhang,et al.  The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis , 2017, Oncotarget.

[31]  Christine Nardini,et al.  Acceleration of leukocytes’ epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer , 2017, Oncotarget.

[32]  G. Pentheroudakis,et al.  Current and future biomarkers in colorectal cancer , 2017, Annals of gastroenterology.

[33]  E. Colicino,et al.  Blood Epigenetic Age may Predict Cancer Incidence and Mortality , 2016, EBioMedicine.

[34]  L. Reggiani Bonetti,et al.  Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study , 2015, Gastroenterology research and practice.

[35]  W. Willett,et al.  Proportion of colon cancer attributable to lifestyle in a cohort of US women , 2015, Cancer Causes & Control.

[36]  W. Willett,et al.  Proportion of colon cancer attributable to lifestyle in a cohort of US women , 2015, Cancer Causes & Control.

[37]  A. Chan,et al.  Nutrients, foods, and colorectal cancer prevention. , 2015, Gastroenterology.

[38]  M. Kobor,et al.  DNA methylation and healthy human aging , 2015, Aging cell.

[39]  G. Pfeifer,et al.  Aging and DNA methylation , 2015, BMC Biology.

[40]  E. Riboli,et al.  Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study , 2014, BMC Medicine.

[41]  M. Vinciguerra,et al.  LINE-1 Hypomethylation in Blood and Tissue Samples as an Epigenetic Marker for Cancer Risk: A Systematic Review and Meta-Analysis , 2014, PloS one.

[42]  S. Lawler,et al.  MicroRNAs in cancer: biomarkers, functions and therapy. , 2014, Trends in molecular medicine.

[43]  C. Matthews,et al.  Physical activity and cancer‐specific mortality in the NIH‐AARP Diet and Health Study cohort , 2014, International journal of cancer.

[44]  G. Binefa,et al.  Colorectal cancer: from prevention to personalized medicine. , 2014, World journal of gastroenterology.

[45]  Thomas W. Mühleisen,et al.  Aging of blood can be tracked by DNA methylation changes at just three CpG sites , 2014, Genome Biology.

[46]  J. Issa Aging and epigenetic drift: a vicious cycle. , 2014, The Journal of clinical investigation.

[47]  C. Pritchard,et al.  Molecular Alterations and Biomarkers in Colorectal Cancer , 2014, Toxicologic pathology.

[48]  S. Horvath DNA methylation age of human tissues and cell types , 2013, Genome Biology.

[49]  Andrew E. Teschendorff,et al.  Age-associated epigenetic drift: implications, and a case of epigenetic thrift? , 2013, Human molecular genetics.

[50]  F. Bazzoli,et al.  Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention , 2013, International journal of molecular sciences.

[51]  Sabha Rasool,et al.  A comparative overview of general risk factors associated with the incidence of colorectal cancer , 2013, Tumor Biology.

[52]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[53]  T. Ideker,et al.  Genome-wide methylation profiles reveal quantitative views of human aging rates. , 2013, Molecular cell.

[54]  P. Laird,et al.  Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer , 2012, PloS one.

[55]  F. Sarkar,et al.  Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF , 2012, Journal of Hematology & Oncology.

[56]  X. Shu,et al.  Body Weight, Fat Distribution and Colorectal Cancer Risk: A Report from Cohort Studies of 134 255 Chinese Men and Women , 2012, International Journal of Obesity.

[57]  Robin M. Murray,et al.  Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population , 2012, PLoS genetics.

[58]  F. Slack,et al.  MicroRNAs and their roles in aging , 2012, Journal of Cell Science.

[59]  K. Straif,et al.  Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[60]  F. Slack,et al.  MicroRNA Predictors of Longevity in Caenorhabditis elegans , 2011, PLoS genetics.

[61]  D. Balding,et al.  Epigenome-wide association studies for common human diseases , 2011, Nature Reviews Genetics.

[62]  Jin An,et al.  Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain , 2011, Neurobiology of Aging.

[63]  V. Ambros,et al.  Effect of life history on microRNA expression during C. elegans development. , 2011, RNA.

[64]  E. Olson,et al.  Pervasive roles of microRNAs in cardiovascular biology , 2011, Nature.

[65]  Zachary Pincus,et al.  MicroRNAs Both Promote and Antagonize Longevity in C. elegans , 2010, Current Biology.

[66]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

[67]  R. Lambert,et al.  The dimensions of the CRC problem. , 2010, Best practice & research. Clinical gastroenterology.

[68]  Nianxiang Zhang,et al.  Widespread and Tissue Specific Age-related Dna Methylation Material Supplemental Related Content a Hallmark of Cancer Age-dependent Dna Methylation of Genes That Are Suppressed in Stem Cells Is , 2022 .

[69]  M. Fraga,et al.  The role of epigenetics in aging and age-related diseases , 2009, Ageing Research Reviews.

[70]  B. Christensen,et al.  Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context , 2009, PLoS genetics.

[71]  Edward Giovannucci,et al.  Cigarette smoking and colorectal cancer incidence and mortality: Systematic review and meta‐analysis , 2009, International journal of cancer.

[72]  Monica Driscoll,et al.  MicroRNAs in C. elegans Aging: Molecular Insurance for Robustness? , 2009, Current genomics.

[73]  M. Yamakuchi,et al.  MiR-34, SIRT1, and p53: The feedback loop , 2009, Cell cycle.

[74]  W. Grady,et al.  Genomic and epigenetic instability in colorectal cancer pathogenesis. , 2008, Gastroenterology.

[75]  M. Yamakuchi,et al.  miR-34a repression of SIRT1 regulates apoptosis , 2008, Proceedings of the National Academy of Sciences.

[76]  O. Maes,et al.  Murine microRNAs implicated in liver functions and aging process , 2008, Mechanisms of Ageing and Development.

[77]  Manel Esteller,et al.  Epigenetics and aging: the targets and the marks. , 2007, Trends in genetics : TIG.

[78]  F. Slack,et al.  A Developmental Timing MicroRNA and Its Target Regulate Life Span in C. elegans , 2005, Science.

[79]  J. Prendergast,et al.  Germline susceptibility to colorectal cancer due to base-excision repair gene defects. , 2005, American journal of human genetics.

[80]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[81]  J. Campisi Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors , 2005, Cell.

[82]  Edward Giovannucci,et al.  Modifiable risk factors for colon cancer. , 2002, Gastroenterology clinics of North America.

[83]  H. Warner Support for basic gerontological research in the USA , 2001, Experimental Gerontology.

[84]  C. Boland,et al.  Colorectal cancer prevention and treatment. , 2000, Gastroenterology.

[85]  J. Herman,et al.  CpG island methylator phenotype in colorectal cancer. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[86]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[87]  E. Rimm,et al.  Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men , 2004, Cancer Causes & Control.

[88]  Hong Ma,et al.  [Biomarkers of aging]. , 2002, Sheng li ke xue jin zhan [Progress in physiology].

[89]  S. Baylin,et al.  Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon , 1994, Nature Genetics.

[90]  J. Hardcastle,et al.  Colorectal cancer , 1993, Europe Against Cancer European Commission Series for General Practitioners.