Huntington’s disease as a protective factor for non-melanoma skin cancer: A retrospective cohort study using the TriNetX dataset.

e21585 Background: Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the encoded protein huntingtin (HTT). Patients exhibit cognitive decline, psychiatric symptoms, and distinctive movement patterns. Previous studies, such as Sørensen et al. and Hamshere et al. have found a reduced incidence of certain cancers in this patient population; data from Murmann et al. show that the mutated HTT molecules are toxic to cancer cells but not healthy cells. However, the association with non-melanoma skin cancer (NMSC) has not been specifically studied. We aimed to investigate HD’s association with such skin cancers. Methods: The TriNetX (Cambridge, MA) US network was utilized to conduct a retrospective cohort study. The exposed group was defined using the ICD-10 code for individuals diagnosed with HD. All diagnoses of NMSC were identified in the time interval after HD diagnosis. The controls included patients who had undergone at least one general outpatient annual physical examination and had no documented history of HD, as identified using ICD-10 codes. We performed adjusted analyses with 1:1 propensity score matching between cohorts for age at index, sex, black and white race, and ethnicity. Results: Of 114,457,565 individuals in the US network, 11,203 met HD diagnosis criteria. 10,326 were included after matching to unexposed. Individuals with HD were less likely to have a diagnosis of SCC compared to those without (RR: 0.18, 95% CI: 0.112,0.29, p<0.0001). There was also a statistically significant decrease in having a diagnosis of BCC (RR: 0.223, 95% CI: 0.159,0.312, p<0.0001). Conclusions: Our study results suggest that patients with HD may have a significantly reduced risk of subsequent NMSC diagnosis. These conclusions support the previous findings of reduced cancer incidence in this subpopulation and the potential protective effects of the mutated huntingtin protein. Given our conclusions, further studies into the associations of HD with various subtypes of cancers and subgroups of patients should be explored and better characterized. In addition, our study supports the emerging idea of leveraging HD insight for neoplastic therapeutic discovery.