Dataset Information

Longitudinal study of leukocyte DNA methylation and biomarkers for cancer risk in older adults.

ABSTRACT: Background:Changes in DNA methylation over the course of life may provide an indicator of risk for cancer. We explored longitudinal changes in CpG methylation from blood leukocytes, and likelihood of future cancer diagnosis. Methods:Peripheral blood samples were obtained at baseline and at follow-up visit from 20 participants in the Health, Aging and Body Composition prospective cohort study. Genome-wide CpG methylation was assayed using the Illumina Infinium Human MethylationEPIC (HM850K) microarray. Results:Global patterns in DNA methylation from CpG-based analyses showed extensive changes in cell composition over time in participants who developed cancer. By visit year 6, the proportion of CD8+ T-cells decreased (p-value?=?0.02), while granulocytes cell levels increased (p-value?=?0.04) among participants diagnosed with cancer compared to those who remained cancer-free (cancer-free vs. cancer-present: 0.03?±?0.02 vs. 0.003?±?0.005 for CD8+ T-cells; 0.52?±?0.14 vs. 0.66?±?0.09 for granulocytes). Epigenome-wide analysis identified three CpGs with suggestive p-values ?10-?5 for differential methylation between cancer-free and cancer-present groups, including a CpG located in MTA3, a gene linked with metastasis. At a lenient statistical threshold (p-value ?3?×?10-?5), the top 10 cancer-associated CpGs included a site near RPTOR that is involved in the mTOR pathway, and the candidate tumor suppressor genes REC8, KCNQ1, and ZSWIM5. However, only the CpG in RPTOR (cg08129331) was replicated in an independent data set. Analysis of within-individual change from baseline to Year 6 found significant correlations between the rates of change in methylation in RPTOR, REC8 and ZSWIM5, and time to cancer diagnosis. Conclusion:The results show that changes in cellular composition explains much of the cross-sectional and longitudinal variation in CpG methylation. Additionally, differential methylation and longitudinal dynamics at specific CpGs could provide powerful indicators of cancer development and/or progression. In particular, we highlight CpG methylation in the RPTOR gene as a potential biomarker of cancer that awaits further validation.

SUBMITTER: Bartlett AH

PROVIDER: S-EPMC6537435 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Longitudinal study of leukocyte DNA methylation and biomarkers for cancer risk in older adults.

Bartlett Alexandra H AH Liang Jane W JW Sandoval-Sierra Jose Vladimir JV Fowke Jay H JH Simonsick Eleanor M EM Johnson Karen C KC Mozhui Khyobeni K

Biomarker research 20190528

<h4>Background</h4>Changes in DNA methylation over the course of life may provide an indicator of risk for cancer. We explored longitudinal changes in CpG methylation from blood leukocytes, and likelihood of future cancer diagnosis.<h4>Methods</h4>Peripheral blood samples were obtained at baseline and at follow-up visit from 20 participants in the Health, Aging and Body Composition prospective cohort study. Genome-wide CpG methylation was assayed using the Illumina Infinium Human MethylationEPIC ...[more]

PMID: 31149338

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Project description:BackgroundResearch on aging has consistently demonstrated an increased chance of survival for older adults who are integrated into rich networks of social relationships. Theoretical explanations state that personal networks offer indirect psychosocial and direct physiological pathways. We investigate whether effects on and pathways to mortality risk differ between functional and structural characteristics of the personal network. The objective is to inquire which personal network characteristics are the best predictors of mortality risk after adjustment for mental, cognitive and physical health.Methods and findingsEmpirical tests were carried out by combining official register information on mortality with data from the Longitudinal Aging Study Amsterdam (LASA). The sample included 2,911 Dutch respondents aged 54 to 85 at baseline in 1992 and six follow-ups covering a time span of twenty years. Four functional characteristics (emotional and social loneliness, emotional and instrumental support) and four structural characteristics (living arrangement, contact frequency, number of contacts, number of social roles) of the personal network as well as mental, cognitive and physical health were assessed at all LASA follow-ups. Statistical analyses comprised of Cox proportional hazard regression models. Findings suggest differential effects of personal network characteristics on survival, with only small gender differences. Mortality risk was initially reduced by functional characteristics, but disappeared after full adjustment for the various health variables. Mortality risk was lowest for older adults embedded in large (HR = 0.986, 95% CI 0.979-0.994) and diverse networks (HR = 0.948, 95% CI 0.917-0.981), and this effect continued to show in the fully adjusted models.ConclusionsFunctional characteristics (i.e. emotional and social loneliness) are indirectly associated with a reduction in mortality risk, while structural characteristics (i.e. number of contacts and number of social roles) have direct protective effects. More research is needed to understand the causal mechanisms underlying these relations.

Dataset Information

Longitudinal study of leukocyte DNA methylation and biomarkers for cancer risk in older adults.

Publications

Longitudinal study of leukocyte DNA methylation and biomarkers for cancer risk in older adults.

Similar Datasets

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