scholarly journals Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 394
Author(s):  
Nazlisadat Seyed Seyed Khoei ◽  
Robert Carreras-Torres ◽  
Neil Murphy ◽  
Marc J. Gunter ◽  
Paul Brennan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Hodgkin’S Lymphoma ◽  
Mendelian Randomization ◽  
Hodgkin's Lymphoma ◽  
Squamous Cell Lung Cancer ◽  
Phenotypic Variance ◽  
A Genome

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.

scholarly journals Leisure Sedentary Behavior and Risk of Lung Cancer: A Two-Sample Mendelian Randomization Study and Mediation Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Gao ◽  
Jiarui Mi ◽  
Zhengye Liu ◽  
Qibin Song
Keyword(s):  
Lung Cancer ◽  
Sedentary Behavior ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Computer Use ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Squamous Cell Lung Cancer ◽  
Television Watching ◽  
Smoking Quantity

Leisure sedentary behavior, especially television watching, has been previously reported as associated with the risk of lung cancer in observational studies. This study aims to evaluate the causal association with two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms associated with leisure television watching, computer use, and driving were extracted from genome-wide association studies. Summary-level results of lung cancer overall and histological types were obtained from International Lung Cancer Consortium (ILCCO). In univariable MR using inverse-variance-weighted method, we observed causal effects of television watching on lung cancer [OR, 1.89, 95% confidence interval (CI), 1.41, 2.54; p = 2.33 × 10−5], and squamous cell lung cancer (OR, 2.37, 95% CI, 1.58, 3.55; p = 3.02 × 10−5), but not on lung adenocarcinoma (OR, 1.40, 95% CI, 0.94, 2.09; p = 0.100). No causal effects of computer use and driving on lung cancer were observed. Television watching significantly increased the exposure to several common risk factors of lung cancer. The associations of television watching with lung cancer and squamous cell lung cancer were compromised after adjusting for smoking quantity with multivariable MR. Our mediation analyses estimated indirect effects of television watching on lung cancer (beta, 0.31, 95% CI, 0.13, 0.52; p = 6.64 × 10−4) and squamous cell lung cancer (beta, 0.33, 95% CI, 0.14, 0.53, p = 4.76 × 10−4) mediated by smoking quantity. Our findings indicate that television watching is positively correlated with the risk of lung cancer, potentially mediated through affecting smoking quantity.

scholarly journals Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer

2008 ◽  
Vol 7 (1) ◽  
pp. 62 ◽  
Author(s):  
Paul P Anglim ◽  
Janice S Galler ◽  
Michael N Koss ◽  
Jeffrey A Hagen ◽  
Sally Turla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Squamous Cell Lung Cancer

scholarly journals Pembrolizumab‐induced pancytopenia in a patient with squamous cell lung cancer

2020 ◽  
Vol 11 (9) ◽  
pp. 2731-2735 ◽  
Author(s):  
Yuriko Ueki ◽  
Manabu Suzuki ◽  
Yuriko Horikawa ◽  
Hiromu Watanabe ◽  
Yoh Yamaguchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Squamous Cell Lung Cancer
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