| Literature DB >> 33671849 |
Nazlisadat Seyed Khoei1, Robert Carreras-Torres2, Neil Murphy3, Marc J Gunter3, Paul Brennan4, Karl Smith-Byrne4, Daniela Mariosa4, James Mckay4, Tracy A O'Mara5, Ruth Jarrett6, Henrik Hjalgrim7,8, Karin E Smedby9,10, Wendy Cozen11, Kenan Onel12, Arjan Diepstra13, Karl-Heinz Wagner1, Heinz Freisling3.
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.Entities:
Keywords: Mendelian randomization; UGT1A1; bilirubin; cancer risk
Year: 2021 PMID： 33671849 PMCID： PMC7918902 DOI： 10.3390/cells10020394
Source DB: PubMed Journal: Cells ISSN： 2073-4409 Impact factor: 6.600