Stochastic epigenetic mutations are associated with risk of breast cancer, lung cancer, and mature b-cell neoplasms

A Gagliardi; PA Dugue; TH Nøst; MC Southey; DD Buchanan; DF Schmidt; E Makalic; AM Hodge; DR English; NW Doo; JL Hopper; G Severi; L Baglietto; A Naccarati; S Tarallo; L Pace; V Krogh; D Palli; S Panico; C Sacerdote; R Tumino; E Lund; GG Giles; B Pardini; TM Sandanger; RL Milne; P Vineis; S Polidoro; G Fiorito

Journal article

Stochastic epigenetic mutations are associated with risk of breast cancer, lung cancer, and mature b-cell neoplasms

A Gagliardi, PA Dugue, TH Nøst, MC Southey, DD Buchanan, DF Schmidt, E Makalic, AM Hodge, DR English, NW Doo, JL Hopper, G Severi, L Baglietto, A Naccarati, S Tarallo, L Pace, V Krogh, D Palli, S Panico, C Sacerdote Show all

Cancer Epidemiology Biomarkers and Prevention | AMER ASSOC CANCER RESEARCH | Published : 2020

DOI: 10.1158/1055-9965.EPI-20-0451

Abstract

Background: Age-related epigenetic dysregulations are associated with several diseases, including cancer. The number of stochastic epigenetic mutations (SEM) has been suggested as a biomarker of life-course accumulation of exposure-related DNA damage; however, the predictive role of SEMs in cancer has seldom been investigated. Methods: A SEM, at a given CpG site, was defined as an extreme outlier of DNA methylation value distribution across individuals. We investigated the association of the total number of SEMs with the risk of eight cancers in 4,497 case-control pairs nested in three prospective cohorts. Furthermore, we investigated whether SEMs were randomly distributed across the genome ..

View full abstract

University of Melbourne Researchers

Pierre-Antoine Dugue Author

Melissa Southey Author

Daniel Buchanan Author

Daniel Schmidt Author Melbourne School of Population and Global Health

Related Projects (8)

Epidemiology of chronic disease, health interventions and DNA studies

Methylation of DNA and colorectal cancer

Methylation of DNA involves a change to the chemical composition of DNA. It can affect the function of genes and normal methylation is essen..

MOLECULAR BIOLOGY OF GASTRIC CANCER

We will investigate whether there are particular patterns of DNA methylation in people who develop gastric cancer. This could provide a mean..

A PROSPECTIVE STUDY OF THE INFLUENCE OF HEALTH - RELATED LIFESTYLE FACTORS ON DNA METHYLATION

It is known that DNA methylation can lead to disease. We aim to discover what causes DNA methylation to change. This could open the way for ..

PRECISION PUBLIC HEALTH FOR MAJOR CANCERS - NOVEL APPROACHES TO BUILDING THE GENETIC, EPIGENETIC AND LIFESTYLE KNOWLEDGE BASE FOR ASSESSING RISK AND PROGNOSIS

The Program of research seeks to increase our understanding of cancer risk. We will use our large collections of population and family-based..

THE HEALTH 2020 COHORT STUDY (HEALTH 2020)

Our aim is to develop appropriate infrastructures necessary to facilitate access by researchers to the accumulated data, including questionn..

METHYLATION AS A RISK FACTOR FOR PROSTATE CANCER

DNA methylation is a process that plays a critical role throughout life by altering the expression of genes. We aim to investigate the poten..

METHYLATION AND THE RISK OF UROTHELIAL CELL CANCER

Why don’t we run prevention programs for urinary tract cancers like we do for others? It’s because we don’t know which lifestyle factors, ex..

Grants

Awarded by Cancer Council Victoria

Funding Acknowledgements

The authors are very thankful to Dr. Akram Ghantous (IARC, Lyon, France) for the methylation analyses of PEM-Turin study, produced within the Exposomics EC FP7 grant (grant agreement no. 308610, to P. Vineis). The results here are, in part, based upon data generated by TCGA research network: https://www.cancer.gov/tcga.The EPIC Italy component of this research was supported by European Commission grant no. 633666, awarded to P. Vineis, and by the AIRC grant (Progetto IG 2013 N.14410, to C. Sacerdote) for part of the DNA methylation experiments. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS component of the work was funded by the Australian National Health and Medical Research Council, including grants 1106016 (to G.G. Giles); 1011618 (to L. Baglietto); 1026892 (to M.C. Southey); 1027505 (to D.R. English); 1050198 and 1087683 (to A.M. Hodge); 1088405 (to R.L. Milne); and 1043616, 209057, 396414, and 1074383 (to G.G. Giles). Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. TheNOWACcomponent of the work was supported by the European Research Council Advanced Researcher grant, 2008: Transcriptomics in cancer research (grant no. ERC-2008-AdG, to E. Lund).