Genetically raised circulating bilirubin levels and risk of ten cancers: A mendelian randomization study
- Autor(en)
- Nazlisadat Seyed Khoei, Robert Carreras-Torres, Neil Murphy, Marc Gunter, Paul Brennan, Karl Smith-Byrne, Daniela Mariosa, James Mckay, Tracy A. O’Mara, Ruth Jarrett, Henrik Hjalgrim, Karin E. Smedby, Wendy Cozen, Kenan Onel, Arjan Diepstra, Karl-Heinz Wagner, Heinz Freisling
- Abstrakt
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 glucuronosyltransfer-ase1A1 (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.
- Organisation(en)
- Department für Ernährungswissenschaften
- Externe Organisation(en)
- International Agency for Research on Cancer (IARC-WHO), Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, University of Glasgow, Statens Serum Institut, Karolinska Institute, University of Southern California, Icahn School of Medicine at Mount Sinai, New York, University of Groningen, Bellvitge Biomedical Research Institute (IDIBELL)
- Journal
- Cells
- Band
- 10
- Seiten
- 1-15
- Anzahl der Seiten
- 15
- ISSN
- 2073-4409
- DOI
- https://doi.org/10.3390/cells10020394
- Publikationsdatum
- 02-2021
- Peer-reviewed
- Ja
- ÖFOS 2012
- 303007 Epidemiologie
- Schlagwörter
- ASJC Scopus Sachgebiete
- Medicine(all)
- Sustainable Development Goals
- SDG 3 – Gesundheit und Wohlergehen
- Link zum Portal
- https://ucrisportal.univie.ac.at/de/publications/genetically-raised-circulating-bilirubin-levels-and-risk-of-ten-cancers-a-mendelian-randomization-study(5408a2fb-d96d-44bc-a6b2-e883891f7d2e).html