F018 Investigating the factors influencing cancer risk in Huntington’s disease

<h3>Background</h3> Individuals living with Huntington’s Disease (HD) have previously been found to have a reduced incidence of cancer, compared to the general population. <h3>Aims</h3> To investigate 1) how the incidence of cancer in HD varies by cancer type, geographical region and HD disease stage, 2) whether CAG length and genetic risk for cancer are associated with cancer in HD. <h3>Methods</h3> We used 19340 individuals from Enroll-PDS6 with an expanded CAG repeat (4986 pre-manifest, 14354 manifest), 931 with cancer. By using GLOBOCAN estimates of cancer risk (for given age, sex, cancer type and region), we obtained the expected number of cancer cases in the sample. Comparing this to the observed counts, we estimated standardised incidence rates for cancer in Enroll-PDS6 (SIR=observed/expected). Cancer genetic risk was estimated by polygenic risk scores (PRS) from publicly available cancer studies. We tested whether these PRS were associated with cancer using logistic regression and survival analyses. <h3>Results</h3> Reduced incidence of cancer was observed in HD (SIR=0.52), with similar results for individual regions. SIR was higher in pre-manifest cases (SIR=0.73) than manifest (SIR=0.49) and further decreases at later disease stages. All cancer types had SIR&lt;1, except for non-melanoma skin cancer. PRS for breast and prostate cancers were significantly associated with these cancers, but not with other types of cancer. <h3>Conclusions</h3> We replicate the previously observed reduction in cancer incidence in HD, and show that it holds across regions, sexes and most cancer types. Interestingly, we find that the reduction in cancer risk increases with advancing disease stage.