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Association between methylation quantitative trait loci and colorectal cancer risk, survival and cancer recurrence

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机构: [1]Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK. [2]Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. [3]School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [4]Danish Institute for Advanced Study, Department of Public Health, University of Southern Denmark, Odense, Denmark. [5]Colon Cancer Genetics Group, Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. [6]Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [7]Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, UK.
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Epigenetic changes contribute to colorectal cancer (CRC) pathogenesis. We investigated whether methylation quantitative trait loci (mQTLs) are associated with CRC risk, survival and recurrence.Using a well-characterised Scottish case-control study (6821 CRC cases, 14,692 controls), we derived 118,982 mQTLs based on the Genetics of DNA Methylation Consortium (GoDMC). Association analysis between mQTLs and CRC risk, survival and recurrence was performed using logistic regression or Cox models respectively. Additionally, colocalisation analysis was performed.19 mQTLs within 10 distinct genomic regions were associated with CRC risk. Two novel regions were mapped to MDGA2 (p value =  3.0 × 10 - 6 ) and STARD3 (p value =  5.6 × 10 - 6 ). Four regions mapped to POU5F1B, POU2AF2 (c11orf53)/POU2AF3 (COLCA2), GREM1 and CABLES2 were previously identified. Four regions mapped to PPA2, PANDAR/LAP3P2, POU6F1 and CTIF contained SNPs previously identified by CRC GWAS but with SNPs annotated to different genes. We found no evidence that any of the 19 mQTLs associated with CRC risk influenced survival or recurrence after FDR correction. Colocalisation analysis suggested that in three of the ten regions the causal variants were shared for methylation and CRC risk.This study adds to the repertoire of CRC genes. However, we found no associations between methylation and CRC survival or recurrence.© 2025. The Author(s).

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大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
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第一作者机构: [1]Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
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