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

Liesel M. Fitzgerald; Haroon Naeem; Enes Makalic; Daniel F. Schmidt; James G Dowty; Jihoon E. Joo; Chol-Hee Jung; Julie K Bassett; Pierre Antoine Dugue; Jessica Chung; Andrew Lonie; Roger L Milne; Ee Ming Wong; John L. Hopper; Dallas R. English; Gianluca Severi; Laura Baglietto; John Pedersen; Graham G. Giles; Melissa C. Southey

doi:10.1002/pros.23289

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

Liesel M. Fitzgerald, Haroon Naeem, Enes Makalic, Daniel F. Schmidt, James G Dowty, Jihoon E. Joo, Chol-Hee Jung, Julie K Bassett, Pierre Antoine Dugue, Jessica Chung, Andrew Lonie, Roger L Milne, Ee Ming Wong, John L. Hopper, Dallas R. English, Gianluca Severi, Laura Baglietto, John Pedersen, Graham G. Giles, Melissa C. Southey

Research output: Contribution to journal › Article › Research › peer-review

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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.

Original language	English
Pages (from-to)	471-478
Number of pages	8
Journal	The Prostate
Volume	77
Issue number	5
DOIs	https://doi.org/10.1002/pros.23289
Publication status	Published - 1 Apr 2017
Externally published	Yes

Keywords

biomarker
DNA methylation
HM450K array
peripheral blood
prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/pros.23289

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Fitzgerald, L. M., Naeem, H., Makalic, E., Schmidt, D. F., Dowty, J. G., Joo, J. E., Jung, C-H., Bassett, J. K., Dugue, P. A., Chung, J., Lonie, A., Milne, R. L., Wong, E. M., Hopper, J. L., English, D. R., Severi, G., Baglietto, L., Pedersen, J., Giles, G. G., & Southey, M. C. (2017). Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study. The Prostate, 77(5), 471-478. https://doi.org/10.1002/pros.23289

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

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.",

keywords = "biomarker, DNA methylation, HM450K array, peripheral blood, prostate cancer",

author = "Fitzgerald, {Liesel M.} and Haroon Naeem and Enes Makalic and Schmidt, {Daniel F.} and Dowty, {James G} and Joo, {Jihoon E.} and Chol-Hee Jung and Bassett, {Julie K} and Dugue, {Pierre Antoine} and Jessica Chung and Andrew Lonie and Milne, {Roger L} and Wong, {Ee Ming} and Hopper, {John L.} and English, {Dallas R.} and Gianluca Severi and Laura Baglietto and John Pedersen and Giles, {Graham G.} and Southey, {Melissa C.}",

year = "2017",

month = apr,

day = "1",

doi = "10.1002/pros.23289",

language = "English",

volume = "77",

pages = "471--478",

journal = "The Prostate",

issn = "0270-4137",

publisher = "John Wiley & Sons",

number = "5",

}

Fitzgerald, LM, Naeem, H, Makalic, E, Schmidt, DF, Dowty, JG, Joo, JE, Jung, C-H, Bassett, JK, Dugue, PA, Chung, J, Lonie, A, Milne, RL, Wong, EM, Hopper, JL, English, DR, Severi, G, Baglietto, L, Pedersen, J, Giles, GG & Southey, MC 2017, 'Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study', The Prostate, vol. 77, no. 5, pp. 471-478. https://doi.org/10.1002/pros.23289

TY - JOUR

T1 - Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study

AU - Fitzgerald, Liesel M.

AU - Naeem, Haroon

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Dowty, James G

AU - Joo, Jihoon E.

AU - Jung, Chol-Hee

AU - Bassett, Julie K

AU - Dugue, Pierre Antoine

AU - Chung, Jessica

AU - Lonie, Andrew

AU - Milne, Roger L

AU - Wong, Ee Ming

AU - Hopper, John L.

AU - English, Dallas R.

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Pedersen, John

AU - Giles, Graham G.

AU - Southey, Melissa C.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - biomarker

KW - DNA methylation

KW - HM450K array

KW - peripheral blood

KW - prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85013393349&partnerID=8YFLogxK

U2 - 10.1002/pros.23289

DO - 10.1002/pros.23289

M3 - Article

C2 - 28116812

AN - SCOPUS:85013393349

VL - 77

SP - 471

EP - 478

JO - The Prostate

JF - The Prostate

SN - 0270-4137

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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