The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis - PubMed (original) (raw)

Xianlei Cai et al. Sci Rep. 2024.

Abstract

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Keywords: Digestive system cancers; Lifestyle; Mendelian randomization; Metabolic comorbidities; Physical conditions; Risk factor.

© 2024. The Author(s).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Figure 1

Flowchart of the data collection, processing, and analysis procedures of this study.

Figure 2

Figure 2

Summary results of this study.

Figure 3

Figure 3

Causal effects of 19 metabolic risk factors on EC estimated by MR analyses.

Figure 4

Figure 4

Causal effects of 19 metabolic risk factors on GC estimated by MR analyses.

Figure 5

Figure 5

Causal effects of 19 metabolic risk factors on CRC estimated by MR analyses.

Figure 6

Figure 6

Causal effects of 19 metabolic risk factors on HCC estimated by MR analyses.

Figure 7

Figure 7

Causal effects of 19 metabolic risk factors on BTC estimated by MR analyses.

Figure 8

Figure 8

Causal effects of 19 metabolic risk factors on PC estimated by MR analyses.

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