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Processed meat, red meat, white meat, and digestive tract cancers: A two-sample Mendelian randomization study
Zhangjun Yun1, Mengdie Nan1, Xiao Li1
1Department of Hematology and Oncology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Background:
Previous observational studies suggested inconsistent insights on the associations between meat intake and the risk of digestive tract cancers (DCTs). The causal effect of meat intake on DCTs is unclear.
Methods:
Two-sample Mendelian randomization (MR) was performed based on genome-wide association studies (GWAS) summary data from UK Biobank and FinnGen to evaluate the causal effect of meat intake [processed meat, red meat (pork, beef, and lamb), and white meat (poultry)] on DCTs (esophageal, stomach, liver, biliary tract, pancreatic, and colorectal cancers). The causal effects were estimated using a primary analysis that employed inverse-variance weighting (IVW) and complementary analysis that utilized MR-Egger weighted by the median. A sensitivity analysis was conducted using the Cochran Q statistic, a funnel plot, the MR-Egger intercept, and a leave-one-out approach. MR-PRESSO and Radial MR were performed to identify and remove outliers. To demonstrate direct causal effects, multivariable MR (MVMR) was applied. In addition, risk factors were introduced to explore potential mediators of the relationship between exposure and outcome.
Results:
The results of the univariable MR analysis indicated that genetically proxied processed meat intake was associated with an increased risk of colorectal cancer [IVW: odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.07-4.19; P = 0.031]. The causal effect is consistent in MVMR (OR = 3.85, 95% CI 1.14-13.04; P = 0.030) after controlling for the influence of other types of exposure. The body mass index and total cholesterol did not mediate the causal effects described above. There was no evidence to support the causal effects of processed meat intake on other cancers, except for colorectal cancer. Similarly, there is no causal association between red meat, white meat intake, and DCTs.
Conclusions:
Our study reported that processed meat intake increases the risk of colorectal cancer rather than other DCTs. No causal relationship was observed between red and white meat intake and DCTs.
Insights
Processed meat intake increases colorectal cancer risk, but not other digestive tract cancers. Red and white meat consumption showed no causal link to digestive tract cancers in this study.
Area of Science:
- Genetics
- Epidemiology
- Nutritional Science
Background:
- Observational studies show inconsistent associations between meat consumption and digestive tract cancers (DCTs).
- The causal relationship between meat intake and DCTs remains unclear, necessitating further investigation.
Purpose of the Study:
- To investigate the causal effect of processed, red, and white meat intake on various digestive tract cancers.
- To clarify the role of meat consumption in the etiology of esophageal, stomach, liver, biliary tract, pancreatic, and colorectal cancers.
Main Methods:
- Two-sample Mendelian randomization (MR) using genome-wide association studies (GWAS) data.
- Primary analysis with inverse-variance weighting (IVW) and complementary MR-Egger analysis.
- Sensitivity analyses including MR-PRESSO and multivariable MR (MVMR) to assess robustness and explore mediation.
Main Results:
- Processed meat intake showed a causal association with an increased risk of colorectal cancer (OR = 2.12, P = 0.031).
- This association remained significant in MVMR analysis (OR = 3.85, P = 0.030) after accounting for other meat types.
- No causal effects were found for processed meat on other DCTs, nor for red or white meat on any DCTs.
Conclusions:
- Processed meat consumption is causally linked to an increased risk of colorectal cancer.
- Red and white meat intake do not appear to have a causal relationship with digestive tract cancers.
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