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T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis.
An, Ni; Zhang, Yu; Sha, Zhilin; Xu, Zhen; Liu, Xiuzhen.
Afiliação
  • An N; Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Zhang Y; No.91126 Military Hospital of Chinese PLA, Dalian, China.
  • Sha Z; Department I of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • Xu Z; Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • Liu X; Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Oncol ; 14: 1327154, 2024.
Article em En | MEDLINE | ID: mdl-38947888
ABSTRACT

Introduction:

Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included.

Methods:

Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively.

Results:

T2DM is associated with a reduced risk of esophageal (OR 0.77, 95% CI 0.71 to 0.83, P< 0.001), gastric (OR 0.87, 95% CI 0.84 to 0.90, P< 0.001) and colorectal cancer (OR 0.88, 95% CI 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR 0.92, 95% CI 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR 1.92, 95% CI 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI 0.65 to 0.99, P=0.044).

Conclusion:

T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Oncol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Oncol Ano de publicação: 2024 Tipo de documento: Article