Heritable methylation marks associated with breast and prostate cancer risk

Pierre Antoine Dugué, James G. Dowty, Jihoon E. Joo, Ee M. Wong, Enes Makalic, Daniel F. Schmidt, Dallas R. English, John L. Hopper, John Pedersen, Gianluca Severi, Robert J. MacInnis, Roger L. Milne, Graham G. Giles, Melissa C. Southey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. Methods: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. Results: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. Conclusions: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalProstate
Volume78
Issue number13
DOIs
Publication statusPublished - 15 Sep 2018

Keywords

  • aggressive prostate cancer
  • CLGN
  • DNA methylation
  • prostate cancer
  • VTRNA2-1

Cite this

Dugué, Pierre Antoine ; Dowty, James G. ; Joo, Jihoon E. ; Wong, Ee M. ; Makalic, Enes ; Schmidt, Daniel F. ; English, Dallas R. ; Hopper, John L. ; Pedersen, John ; Severi, Gianluca ; MacInnis, Robert J. ; Milne, Roger L. ; Giles, Graham G. ; Southey, Melissa C. / Heritable methylation marks associated with breast and prostate cancer risk. In: Prostate. 2018 ; Vol. 78, No. 13. pp. 962-969.
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title = "Heritable methylation marks associated with breast and prostate cancer risk",
abstract = "Background: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. Methods: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95{\%} confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. Results: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. Conclusions: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.",
keywords = "aggressive prostate cancer, CLGN, DNA methylation, prostate cancer, VTRNA2-1",
author = "Dugu{\'e}, {Pierre Antoine} and Dowty, {James G.} and Joo, {Jihoon E.} and Wong, {Ee M.} and Enes Makalic and Schmidt, {Daniel F.} and English, {Dallas R.} and Hopper, {John L.} and John Pedersen and Gianluca Severi and MacInnis, {Robert J.} and Milne, {Roger L.} and Giles, {Graham G.} and Southey, {Melissa C.}",
year = "2018",
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Dugué, PA, Dowty, JG, Joo, JE, Wong, EM, Makalic, E, Schmidt, DF, English, DR, Hopper, JL, Pedersen, J, Severi, G, MacInnis, RJ, Milne, RL, Giles, GG & Southey, MC 2018, 'Heritable methylation marks associated with breast and prostate cancer risk', Prostate, vol. 78, no. 13, pp. 962-969. https://doi.org/10.1002/pros.23654

Heritable methylation marks associated with breast and prostate cancer risk. / Dugué, Pierre Antoine; Dowty, James G.; Joo, Jihoon E.; Wong, Ee M.; Makalic, Enes; Schmidt, Daniel F.; English, Dallas R.; Hopper, John L.; Pedersen, John; Severi, Gianluca; MacInnis, Robert J.; Milne, Roger L.; Giles, Graham G.; Southey, Melissa C.

In: Prostate, Vol. 78, No. 13, 15.09.2018, p. 962-969.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Heritable methylation marks associated with breast and prostate cancer risk

AU - Dugué, Pierre Antoine

AU - Dowty, James G.

AU - Joo, Jihoon E.

AU - Wong, Ee M.

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - English, Dallas R.

AU - Hopper, John L.

AU - Pedersen, John

AU - Severi, Gianluca

AU - MacInnis, Robert J.

AU - Milne, Roger L.

AU - Giles, Graham G.

AU - Southey, Melissa C.

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Background: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. Methods: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. Results: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. Conclusions: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.

AB - Background: DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer. Methods: We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer. Results: Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer. Conclusions: This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.

KW - aggressive prostate cancer

KW - CLGN

KW - DNA methylation

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