BACKGROUND: Global measures of peripheral blood DNA methylation have been associated with risk of some malignancies, including breast, bladder, and gastric cancer. Here, we examined genome-wide measures of peripheral blood DNA methylation in prostate cancer and its non-aggressive and aggressive disease forms. METHODS: We used a matched, case-control study of 687 incident prostate cancer samples, nested within a larger prospective cohort study. DNA methylation was measured in pre-diagnostic, peripheral blood samples using the Illumina Infinium HM450K BeadChip. Genome-wide measures of DNA methylation were computed as the median M-value of all CpG sites and according to CpG site location and regulatory function. We used conditional logistic regression to test for associations between genome-wide measures of DNA methylation and risk of prostate cancer and its subtypes, and by time between blood draw and diagnosis. RESULTS: We observed no associations between the genome-wide measure of DNA methylation based on all CpG sites and risk of prostate cancer or aggressive disease. Risk of non-aggressive disease was associated with higher methylation of CpG islands (OR = 0.80; 95%CI = 0.68–0.94), promoter regions (OR = 0.79; 95%CI = 0.66–0.93), and high density CpG regions (OR = 0.80; 95%CI = 0.68–0.94). Additionally, higher methylation of all CpGs (OR = 0.66; 95%CI = 0.48–0.89), CpG shores (OR = 0.62; 95%CI = 0.45–0.84), and regulatory regions (OR = 0.68; 95% CI = 0.51–0.91) was associated with a reduced risk of overall prostate cancer within 5 years of blood draw but not thereafter. CONCLUSIONS: A reduced risk of overall prostate cancer within 5 years of blood draw and non-aggressive prostate cancer was associated with higher genome-wide methylation of peripheral blood DNA. While these data have no immediate clinical utility, with further work they may provide insight into the early events of prostate carcinogenesis. Prostate 77:471–478, 2017. © 2017 Wiley Periodicals, Inc.

Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study

BAGLIETTO, LAURA;
2017-01-01

Abstract

BACKGROUND: Global measures of peripheral blood DNA methylation have been associated with risk of some malignancies, including breast, bladder, and gastric cancer. Here, we examined genome-wide measures of peripheral blood DNA methylation in prostate cancer and its non-aggressive and aggressive disease forms. METHODS: We used a matched, case-control study of 687 incident prostate cancer samples, nested within a larger prospective cohort study. DNA methylation was measured in pre-diagnostic, peripheral blood samples using the Illumina Infinium HM450K BeadChip. Genome-wide measures of DNA methylation were computed as the median M-value of all CpG sites and according to CpG site location and regulatory function. We used conditional logistic regression to test for associations between genome-wide measures of DNA methylation and risk of prostate cancer and its subtypes, and by time between blood draw and diagnosis. RESULTS: We observed no associations between the genome-wide measure of DNA methylation based on all CpG sites and risk of prostate cancer or aggressive disease. Risk of non-aggressive disease was associated with higher methylation of CpG islands (OR = 0.80; 95%CI = 0.68–0.94), promoter regions (OR = 0.79; 95%CI = 0.66–0.93), and high density CpG regions (OR = 0.80; 95%CI = 0.68–0.94). Additionally, higher methylation of all CpGs (OR = 0.66; 95%CI = 0.48–0.89), CpG shores (OR = 0.62; 95%CI = 0.45–0.84), and regulatory regions (OR = 0.68; 95% CI = 0.51–0.91) was associated with a reduced risk of overall prostate cancer within 5 years of blood draw but not thereafter. CONCLUSIONS: A reduced risk of overall prostate cancer within 5 years of blood draw and non-aggressive prostate cancer was associated with higher genome-wide methylation of peripheral blood DNA. While these data have no immediate clinical utility, with further work they may provide insight into the early events of prostate carcinogenesis. Prostate 77:471–478, 2017. © 2017 Wiley Periodicals, Inc.
2017
Fitzgerald, Liesel M.; Naeem, Haroon; Makalic, Enes; Schmidt, Daniel F.; Dowty, James G.; Joo, Jihoon E.; Jung, Chol Hee; Bassett, Julie K.; Dugue, Pierre Antoine; Chung, Jessica; Lonie, Andrew; Milne, Roger L.; Wong, Ee Ming; Hopper, John L.; English, Dallas R.; Severi, Gianluca; Baglietto, Laura; Pedersen, John; Giles, Graham G.; Southey, Melissa C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/850916
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