Epigenetic alterations of a novel antioxidant gene SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer
| Autor: | Hua Hui Li, Li Fu, Stephen J. Meltzer, Yan Song Wang, Yuriko Mori, Xin Yuan Guan, Jingyi Sheng, Tu Xiong Huang, Ji Xian Xiong, Di Xiang, Binbin Tan, Yan Ru Qin, Jiao Yang, Cui Mian Zeng |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Esophageal Neoplasms Fluorescent Antibody Technique Genome-wide association study Applied Microbiology and Biotechnology Epigenesis Genetic 0302 clinical medicine Promoter Regions Genetic Aged 80 and over education.field_of_study biology Esophageal cancer Middle Aged 3. Good health 030220 oncology & carcinogenesis DNA methylation Female Research Paper Adult Organic Cation Transport Proteins Population Blotting Western Models Biological SLC22A3 Familial ESCC - SLC22A3 - DNA methylation - antioxidant gene -oxidative DNA damage 03 medical and health sciences medicine Humans Genetic Predisposition to Disease Epigenetics Risk factor education Molecular Biology Gene Ecology Evolution Behavior and Systematics Aged business.industry Lentivirus Cell Biology DNA Methylation medicine.disease digestive system diseases 030104 developmental biology Case-Control Studies Cancer research biology.protein business Reactive Oxygen Species Heat-Shock Response Developmental Biology DNA Damage Genome-Wide Association Study |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Esophageal squamous cell carcinoma (ESCC) occurs with the highest frequency in China, especially in the high-risk Northern Chinese. Recent studies have reported that SLC22A3 is significantly downregulated in non-tumor (NT) esophageal tissues from familial ESCC patients compared with those from sporadic ESCC. However, the mechanism of how SLC22A3 regulates familial ESCC remains unknown. In this study, post hoc genome-wide association studies (GWAS) in 496 cases with a family history of upper gastrointestinal tract cancers and 1056 controls were performed and the results revealed that SLC22A3 is a novel susceptibility gene for familial ESCC. Reduced expression of SLC22A3 in NT esophageal tissues from familial ESCC patients significantly correlates with its promoter hypermethylation. Moreover, case-control study of Chinese descendants from different risk areas of China revealed that the methylation of the SLC22A3 gene in peripheral blood leukocyte (PBL) DNA samples could be a risk factor for developing ESCC in this high-risk population. Functional studies showed that SLC22A3 is a novel antioxidant gene, and deregulation of SLC22A3 facilitates heat stress-induced oxidative DNA damage and formation of γ-H2AX foci in normal esophageal epithelial cells. Collectively, we show that epigenetic alterations of SLC22A3 predispose susceptible individuals to increased risk of esophageal cancer. |
| Databáze: | OpenAIRE |
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