The causal effect of hot beverage temperature preference on esophageal cancer risk: a Mendelian randomization study

Previous research has found a link between the temperature of food and beverages and the risk of esophageal cancer (EC). A causal relationship between the two has not been well established. Herein, we used Mendelian randomization (MR) analysis to assess the causal effect of temperature preference for hot beverages on EC risk.

Genome-wide association studies (GWAS) data for hot beverage temperature preference were obtained from the UK biobank. There were 457,873 European and 2,617 East Asian participants included. GWAS data for EC were obtained from the Integrative Epidemiology Unit (IEU) project database. Two datasets from the European population and two datasets from the East Asian population were included. Totally, 4,426 EC cases and 1,202,270 control subjects were included. The "TwoSampleMR" R package was used to conduct a two-sample MR analysis. A random-effect inverse variance weighted (IVW) was used as the main analytical method to estimate the causal effect, and various sensitivity analyses, including MR Egger, weighted median, simple mode, and weighted mode, were used to examine the potential violation of the second and third MR assumptions. Meta-analyses were performed to further confirm the results.

Sixty-eight single nucleotide polymorphisms (SNPs) from the European population and 11 SNPs from the East Asian population were used for MR analysis. No significant causal effect was found between hot beverage temperature preference and EC risk in the European population {for the ieu-b-4960 dataset, inverse variance weighted odds ratio (OR_IVW) =1.00 [95% confidence interval (CI): 0.99-1.00], P=0.54; for the ebi-a-GCST90018841 dataset, OR_IVW =0.35 (95% CI: 0.10-1.29), P=0.12} or in the East Asian population [for the bbj-a-117 dataset, OR_IVW =1.09 (95% CI: 0.80-1.48), P=0.59; for the ebi-a-GCST90018621 dataset, OR_IVW =0.11 (95% CI: 0.82-1.50), P=0.49]. Meta-analyses of the European population datasets and the Asian population datasets showed consistent results.

The current MR analysis provides new genetic evidence for a null causal relationship between hot beverage temperature preference and EC, both in the European population and the East Asian population. Evidence to prevent EC by reducing the intake of hot beverages is insufficient.