Abstract Title:

Longitudinal Study of DNA Methylation of Inflammatory Genes and Cancer Risk.

Abstract Source:

Cancer Epidemiol Biomarkers Prev. 2015 Aug 11. Epub 2015 Aug 11. PMID: 26265203

Abstract Author(s):

Brian Thomas Joyce, Tao Gao, Lei Liu, Yinan Zheng, Siran Liu, Wei Zhang, Frank Penedo, Qi Dai, Joel Schwartz, Andrea A Baccarelli, Lifang Hou

Article Affiliation:

Brian Thomas Joyce


BACKGROUND: Chronic inflammation plays a key role in cancer etiology. DNA methylation modification, one of the epigenetic mechanisms regulating gene expression, is considered a hallmark of cancer. Human and animal models have identified numerous links between DNA methylation and inflammatory biomarkers. Our objective was to prospectively and longitudinally examine associations between methylation of four inflammatory genes and cancer risk.

METHODS: We included 795 Normative Aging Study participants with blood drawn 1-4 times from 1999-2012 (median follow up 10.6 years). Promoter DNA methylation of IL-6, ICAM-1, IFN, and TLR2 in blood leukocytes was measured using pyrosequencing at multiple CpG sites and averaged by gene for data analysis. We used Cox regression models to examine prospective associations of baseline and time-dependent methylation with cancer risk, and compared mean methylation differences over time between cancer cases and cancer-free participants.

RESULTS: Baseline IFN hypermethylation was associated with all-cancer (HR=1.49, p=0.04) and prostate cancer incidence (HR=1.69, p=0.02). Baseline ICAM-1 and IL-6 hypermethylation were associated with prostate cancer incidence (HR=1.43, p=0.02; HR=0.70, p=0.03 respectively). In our time-dependent analyses, IFN hypermethylation was associated with all-cancer (HR=1.79, p=0.007) and prostate cancer (HR=1.57, p=0.03) incidence; and ICAM-1 and IL-6 hypermethylation were associated with prostate cancer incidence (HR=1.39, p=0.02; HR=0.69, p=0.03 respectively). We detected significant ICAM-1 hypermethylation in cancer cases (p=0.0003) 10-13 years pre-diagnosis.

CONCLUSION: Hypermethylation of IFN and ICAM-1 may play important roles in early carcinogenesis, particularly that of prostate cancer.

IMPACT: These methylation changes could inform the development of early detection biomarkers and potential treatments of inflammation-related carcinogenesis.

Study Type : Human Study

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