Associations Between Genetically Predicted Plasma N-Glycans and Prostate Cancer Risk: Analysis of Over 140,000 European Descendants

BACKGROUND: Previous studies suggest a potential link between glycosylation and prostate cancer. To better characterize the relationship between the two, we performed a study to comprehensively evaluate the associations between genetically predicted blood plasma N-glycan levels and prostate cancer risk. METHODS: Using genetic variants associated with N-glycan levels as instruments, we evaluated the associations between levels of 138 plasma N-glycans and prostate cancer risk. We analyzed data of 79,194 cases and 61,112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL. RESULTS: We identified three N-glycans with genetically predicted levels in plasma to be associated with prostate cancer risk after Bonferroni correction. The estimated odds ratios (95% confidence intervals) were 1.29 (1.20–1.40), 0.80 (0.74–0.88), and 0.79 (0.72–0.87) for PGP18, PGP33, and PGP109, respectively, per every one standard deviation increase in genetically predicted levels of N-glycan. However, the instruments for these N-glycans only involved one to two variants. The proportions of variations that can be explained by the instruments range from 1.58% to 2.95% for these three N-glycans. CONCLUSION: We observed associations between genetically predicted levels of three N-glycans PGP18, PGP33, and PGP109 and prostate cancer risk. Given the correlated nature of the N-glycans and that many N-glycans share genetic loci, pleiotropy is a major concern. Future work is warranted to better characterize the relationship between N-glycans and prostate cancer.