The mediating role of blood metabolites in the association between myocardial infarction and cancer risk: An observational and mendelian randomization analysis

TL;DR

This study suggests that heart attacks may lower cancer risk by changing blood metabolite levels, but more research is needed to confirm this.

Contribution

The study identifies specific blood metabolites that may mediate the reduced cancer risk following myocardial infarction.

Findings

Observational analysis found no direct link between MI and cancer.

MR analysis showed MI was associated with reduced cancer incidence.

Increased levels of certain metabolites like dihomo-linoleate and alpha-tocopherol may explain the reduced cancer risk.

Abstract

Myocardial infarction (MI) and cancer are major global public health challenges. Research indicates that they share common risk factors and that physiological changes following MI may affect cancer incidence and progression. However, evidence defining the independent relationship between these conditions is still limited.

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) (2011–2018) using multivariable weighted logistic regression to examine the association between myocardial infarction (MI) and cancer. Additionally, we utilized genome-wide association study (GWAS) summary statistics and conducted Mendelian randomization (MR) to assess potential causal relationships and explore underlying mechanisms. Sensitivity analyses were performed to ensure the robustness of our findings.

A total of 20,859 participants were included in our observational study using NHANES data. Multivariable weighted logistic regression revealed no direct association between MI and cancer (OR=1.161, 95% CI [0.895–1.507], P = 0.261). Interestingly, MR analysis indicated that MI occurrence was associated with a reduced incidence of cancer (OR=0.9497, 95% CI [0.9223–0.9778], P = 0.0005). Furthermore, two-stage MR results suggested this reduction might be mediated by increased blood levels of metabolites that inhibit cancer development, such as dihomo-linoleate (20:2n6) (beta = −0.0050, 95% CI [−0.0027–0.0004], P < 0.0001), alpha-tocopherol (beta = −0.0042, 95% CI [−0.0060–0.0025], P < 0.0001), inosine (beta = −0.0015, 95% CI [−0.0027–0.0004], P = 0.0084), and methyl glucopyranoside (alpha + beta) levels (beta = −0.0006, 95% CI [−0.0010–0.0003], P = 0.0008).

Our integrative analysis suggests that myocardial infarction may be associated with a reduced cancer incidence through potential alterations in blood metabolite profiles, including dihomo-γ-linolenic acid, alpha-tocopherol, and inosine. These findings provide preliminary evidence that warrants further large-scale studies to validate the observed associations and to elucidate the underlying mechanisms.

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