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Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 ± 1.6 versus 22.1 ± 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is characterized by different pathways of carcinogenesis and is a heterogeneous disease with diverse molecular landscapes that reflect histopathological and clinical information. Changes in the DNA methylation status of colon epithelial cells have been identified as critical components in CRC development and appear to be emerging biomarkers for the early detection and prognosis of CRC. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers of CRC. METHODS: We compared the levels and frequencies of DNA methylation in 11 genes (Alu, APC, DAPK, MGMT, MLH1, MINT1, MINT2, MINT31, p16, RGS6, and TFPI2) in colorectal cancer and its precursor adenomatous polyp with normal tissue of healthy subjects using pyrosequencing and then evaluated the clinical value of these genes. RESULTS: Aberrant methylation of Alu, MGMT, MINT2, and TFPI2 genes was progressively accumulated during the normal-adenoma-carcinoma progression. Additionally, CGI methylation occurred either as an adenoma-associated event for APC, MLH1, MINT1, MINT31, p16, and RGS6 or a tumor-associated event for DAPK. Moreover, relatively high levels and frequencies of DAPK, MGMT, and TFPI2 methylation were detected in the peritumoral nonmalignant mucosa of cancer patients in a field-cancerization manner, as compared to normal mucosa from healthy subjects. CONCLUSION: This study identified several biomarkers associated with the initiation and progression of CRC. As novel findings, they may have important clinical implications for CRC diagnostic and prognostic applications. Further large-scale studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-associated mortality due to high incidence and poor survival rates, irrespective of global variations in its biology and treatment. Changes in DNA methylation are frequent in cancer and constitute an important mechanism in tumorigenesis. Normal mucosa of esophagus-specific 1 (NMES1) is expressed in epithelial tissue and is believed to be a tumor suppressor gene. The present study investigated the methylation status of the NMES1 promoter in 178 cases of primary non-small cell lung cancer (NSCLC) by pyrosequencing and evaluated the prognostic value of this methylation. NMES1 methylation-positive tumors above the background threshold for non-malignant tissue were found in 15 cases (8.4%) and were detected exclusively in malignant tissues. In addition, univariate and multivariate analyses showed that methylation-positive patients experienced worse overall survival rate (OSR) compared with methylation-negative patients (adjusted hazard ratio, 2.62; 95% confidence interval, 1.20-5.69; P=0.02). Notably, within the methylation-positive group, patients with strong methylation tended to experience worse OSR compared with those with weak methylation (adjusted hazard ratio, 2.45 vs. 3.05; Ptrend=0.02). These findings suggest that NMES1 may serve an important role in lung cancer pathogenesis, and its methylation could be considered a prognostic marker for NSCLC. Further studies with large numbers of samples are required to confirm this conclusion. [ABSTRACT FROM AUTHOR]

Background: Persistent organic pollutants (POPs), despite their considerably low levels in humans, are an increasing concern for the general populations given their various adverse health problems, including metabolic and carcinogenic effects. DNA methylation deregulation is thought to be a key mechanism in the development of human chronic diseases including cancer. Methods: In an attempt to identify biomarkers monitoring low-dose exposure and hazard, we explored whether organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) may influence the methylation of tumour suppressor gene E-cadherin (CDH1) using peripheral blood cells from 364 healthy Korean subjects. Results: CDH1 methylation was observed in 78.3% of study subjects. Serum concentrations of OCPs or PCBs compounds were higher in CDH1 methylation-positive subjects than in methylation-negative ones. After adjusting for various covariates, the odds ratio of CDH1 methylation of the summary measure of PCBs were 1.0, 2.5 (95% confidence interval: 1.2-5.3), 3.6 (1.6-8.1), 3.6 (1.4-8.6), and 2.5 (1.1-5.7) across quintiles of PCBs (Ptrend = 0.01). The values of OCPs were 1.0, 0.9, 1.2, 2.4 (1.0-5.9), and 1.7 (Ptrend = 0.05). Conclusions: In this exploratory study with a small sample, CDH1 methylation might be served as the epigenetic biomarker associated with POPs exposure and adverse health effect. [ABSTRACT FROM AUTHOR]