Duo Liu1,2, Jingjing Zhu2, Tianying Zhao2,3, Sodbo Sharapov4, Evgeny Tiys4, Lang Wu2. 1. Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China. 2. Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA. 3. Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, USA. 4. Laboratory of Glycogenomics, Institute of Cytology and Genetics, Novosibirsk, Russia.
Abstract
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.
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.
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