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Genetic association of glycemic traits and antihyperglycemic agent target genes with the risk of lung cancer: A Mendelian randomization study

Sun, Wen ; Zhang, Xiaoyu ; Li, Ning ; He, Yan ; Ji, Jianguang LU orcid and Zheng, Deqiang LU (2024) In Diabetes & metabolic syndrome
Abstract
Aims
To evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk.
Methods
Genetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore... (More)
Aims
To evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk.
Methods
Genetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore whether overweight operated as a mediator between antihyperglycemic agents and lung cancer outcomes.
Results
Genetically determined glycated hemoglobin A1c levels were associated with squamous cell lung cancer (OR = 1.78; 95% CI, 1.08-2.92; p = 0.023). The PRKAB1 gene (the target of metformin) was associated with a lower risk of developing lung adenocarcinoma (OR = 0.85; 95% CI, 0.76-0.96; p = 0.006). Further mediation analyses did not support overweight as a mediator between PRKAB1 activation and lung adenocarcinoma.
Conclusion
Our analyses suggest an association of genetically determined abnormal glycemic traits with squamous cell lung cancer. The potential association between PRKAB1 activation and a reduced risk of developing lung adenocarcinoma appears to be independent of the anti-obesity effects of metformin, suggesting that PRKAB1 activation may have a direct protective effect on lung adenocarcinoma development. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Diabetes & metabolic syndrome
article number
103048
publisher
Elsevier
ISSN
1871-4021
DOI
10.1016/j.dsx.2024.103048
language
English
LU publication?
yes
id
791ccb61-1756-49a3-8bc9-6ee6b5fb1403
date added to LUP
2024-06-04 09:44:44
date last changed
2024-06-04 14:59:54
@article{791ccb61-1756-49a3-8bc9-6ee6b5fb1403,
  abstract     = {{Aims<br/>To evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk.<br/>Methods<br/>Genetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore whether overweight operated as a mediator between antihyperglycemic agents and lung cancer outcomes.<br/>Results<br/>Genetically determined glycated hemoglobin A1c levels were associated with squamous cell lung cancer (OR = 1.78; 95% CI, 1.08-2.92; p = 0.023). The PRKAB1 gene (the target of metformin) was associated with a lower risk of developing lung adenocarcinoma (OR = 0.85; 95% CI, 0.76-0.96; p = 0.006). Further mediation analyses did not support overweight as a mediator between PRKAB1 activation and lung adenocarcinoma.<br/>Conclusion<br/>Our analyses suggest an association of genetically determined abnormal glycemic traits with squamous cell lung cancer. The potential association between PRKAB1 activation and a reduced risk of developing lung adenocarcinoma appears to be independent of the anti-obesity effects of metformin, suggesting that PRKAB1 activation may have a direct protective effect on lung adenocarcinoma development.}},
  author       = {{Sun, Wen and Zhang, Xiaoyu and Li, Ning and He, Yan and Ji, Jianguang and Zheng, Deqiang}},
  issn         = {{1871-4021}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{Diabetes & metabolic syndrome}},
  title        = {{Genetic association of glycemic traits and antihyperglycemic agent target genes with the risk of lung cancer: A Mendelian randomization study}},
  url          = {{http://dx.doi.org/10.1016/j.dsx.2024.103048}},
  doi          = {{10.1016/j.dsx.2024.103048}},
  year         = {{2024}},
}