Abstract 6486: Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study

Abstract Introduction: Intracellular cholesterol metabolism plays an important role in prostate cancer progression and emergence of treatment resistance. However, it remains unclear whether serum cholesterol and lipoproteins are associated with prostate cancer outcomes. Studies on serum cholesterol and cancer are often confounded by lifestyle factors such as diet and obesity. A possible solution is to use instrumental variables, such as SNPs predicting serum cholesterol. According to the Mendelian randomization theory, germline SNP distribution is unaffected by confounding variables such as diet and lifestyle factors. Objective: To estimate whether SNPs that predict serum cholesterol and lipoproteins also predict mortality among a cohort of men with prostate cancer. Methods: Our study cohort consisted of 3,241 men diagnosed with prostate cancer between 1996-2015, using data collected by the Finnish Randomized Study of Screening for Prostate Cancer. Blood samples were genotyped by PRACTICAL consortium. A UCSC genome browser was utilized for selecting 85 SNPs in lipid metabolism-associated genes. Dates and causes of deaths between 1996-2015 were obtained from the Statistics Finland's statistics on causes of death. Information on serum cholesterol and lipoprotein measurements were obtained from a regional laboratory database.Scores predicting serum cholesterol, LDL, HDL and triglyceride level by SNP genotype were created using linear regression and lasso regression. Risk of prostate cancer death and overall mortality by level of the SNP risk score were evaluated with multivariable-adjusted Cox regression. Follow-up started at prostate cancer diagnosis and continued until death, emigration or common closing date of Dec 31, 2015.Results: SNP score predicting total cholesterol stratified prostate cancer patients both for disease-specific (HR 1.27, 95% CI 0.49-3.28 for highest tertile vs. lowest) and overall survival (HR 1.43, 95% CI 0.94-2.20, p for trend = 0.077), albeit statistical significance was not reached. Similar survival differences were observed for SNP score predicting triglyceride level, but not for scores predicting LDL or HDL.Conclusions: SNPs predicting serum cholesterol and triglycerides are likely prognostic factors for survival of prostate cancer patients. This suggest serum cholesterol and lipoproteins areimportant in prostate cancer progression. Total cholesterol SNP scoreProstate-cancer specific survival Overall survival Citation Format: Sebastian Boele, Aino Siltari, Paavo Raittinen, Johanna Schleutker, Kimmo Taari, Kirsi Talala, Teuvo Tammela, Anssi Auvinen, Teemu J. Murtola. Single nucleotide polymorphisms that predict serum cholesterol as a prostate cancer prognostic factor - a Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6486.