Causal relationship between serum metabolites and risk of thyroid cancer: a mendelian randomization study

Abstract Background The high incidence of thyroid cancer (TC) has become a significant global medical burden. Our research aims to investigate the relationship between serum metabolites and the onset of TC. Materials and methods We used two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 1,400 serum metabolites and TC. The causal effects were mainly assessed using the inverse variance weighted (IVW) method, wald ratio, and 95% confidence intervals (CI). Sensitivity analyses were performed using Cochran’s Q Test and MR-PRESSO. The MR-Steiger test was applied to examine reverse causal relationships. Additionally, pathway enrichment analysis was conducted for the causal relationships between known metabolites and TC risk. Results Out of 1400 metabolites, 20 were associated with TC. These included ratios of 5 metabolites and 15 individual metabolites (13 known, 2 unknown). Among the 13 known metabolites, 5 were identified as protective factors against TC: 1-palmitoyl-2-oleoyl-GPI (16:0/18:2), 1-palmitoyl-2-oleoyl-GPI (16:0/18:1), aspartic acid, 1-stearoyl-2-oleoyl-GPI (18:0/18:1), and 1-stearoyl-2-oleoyl-GPI (18:0/18:2). The remaining 8 metabolites (phosphocholine, 5-methyluridine (ribosylthymine), (R)-3-hydroxybutyrylcarnitine, dimethyl sulfoxide, isobutyrylcarnitine (C5), glycerol 3-phosphate, lactosyl-n-palmitoylsphingosine (d18:1/16:0), and pregnenolone sulfate (C21H34O5S)) were identified as potential risk factors for an increased likelihood of TC occurrence. Among the protective metabolites, the protective effect of 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2) was most significant (P = 0.0036, Odds ratio (OR) = 0.82, 95% CI [0.72–0.94]). Among the risk factors, phosphocholine was the most significant (P = 0.004, OR = 1.39, 95% CI [1.11–1.74]). Conclusions This study revealed the potential relationship between serum metabolites and TC.