Genetic risk score for cholesteatoma recurrence: using UK Biobank data toward more individualized patient management

Cholesteatoma recurrence is relatively common and often requires repeat surgical interventions, imposing a significant burden on patients and healthcare systems. Although clinical factors such as age, disease aggressiveness, surgical technique, and surgeon experience influence recurrence risk, accurate prediction remains challenging. Genetic Risk Scores (GRS), which aggregate the effects of multiple genetic variants, offer a promising approach to individualized recurrence risk estimation.

To evaluate the contribution of specific genetic variants to cholesteatoma recurrence by constructing a GRS using data from the UK Biobank.

A systematic review of PubMed identified six genes previously associated with cholesteatoma recurrence: KGF (FGF7), KGF-R (FGFR2), MMP9, KRT1, KRT10, and MIF. Corresponding single nucleotide polymorphisms (SNPs) were analyzed using the UK Biobank, a large-scale biomedical database of approximately 500,000 participants. Individuals with recurrent cholesteatoma were identified using ICD-10 code H95.0. SNPs with minor allele frequency <5% or in linkage disequilibrium were excluded. A weighted GRS was calculated by summing the number of risk alleles for each SNP, multiplied by their β coefficients (log odds ratios).

A total of 39 SNPs were included in the final GRS calculation. Among 502,164 UK Biobank participants, 55 individuals were identified with recurrent cholesteatoma. The mean GRS for these individuals was 3.86, compared to 3.72 in the general population, indicating a 15.6% relative increase in genetically determined recurrence risk (OR ≈ 1.156).

This study demonstrates a modest but measurable contribution of genetic variation to cholesteatoma recurrence. While the effect size is limited, future studies with larger cohorts and genome-wide data may improve predictive accuracy. Even at this stage, the GRS may help guide surgical decision-making and follow-up planning, moving toward more personalized management of cholesteatoma.