Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/175497
Title: | Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study |
Author: | Seyed Khoei, Nazlisadat Carreras Torres, Robert Murphy, Neil Gunter, Marc J. Brennan, Paul Smith-Byrne, Karl Mariosa, Daniela McKay, James D. O’Mara, Tracy Jarrett, Ruth Hjalgrim, Henrik Smedby, Karin E. Cozen, Wendy Onel, Kenan Diepstra, Arjan Wagner, Karl-Heinz Freisling, Heinz ECAC Group |
Keywords: | Càncer Antioxidants Factors de risc en les malalties Cancer Antioxidants Risk factors in diseases |
Issue Date: | 15-Feb-2021 |
Publisher: | MDPI |
Abstract: | Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10-8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, P 0.04 and OR 0.64, 95% CI 0.42-0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/cells10020394 |
It is part of: | Cells, 2021, vol. 10, num. 2 |
URI: | http://hdl.handle.net/2445/175497 |
Related resource: | https://doi.org/10.3390/cells10020394 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
cells-10-00394-v2.pdf | 1.18 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License