White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, colorectal, and Ovarian cancer screening trial (PLCO)

Susan R. Sturgeon, J. Richard Pilsner, Kathleen F. Arcaro, Kaoru Ikuma, Haotian Wu, Soon Mi Kim, Nayha Chopra-Tandon, Adam R Karpf, Regina G. Ziegler, Catherine Schairer, Raji Balasubramanian, David A. Reckhow

Research output: Contribution to journalArticle

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Abstract

Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2' deoxycytidine [5-mdC] to 2'-deoxyguanine [dG], assuming [dG]=[5-mdC]+[2'-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results: Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6-1.3), 0.88 (95% CI, 0.6-1.3), and 0.84 (95% CI, 0.6-1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend=.39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion: These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.

Original languageEnglish (US)
Article number94
JournalBreast Cancer Research
Volume19
Issue number1
DOIs
StatePublished - Aug 18 2017

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DNA Methylation
Early Detection of Cancer
Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
5-methyldeoxycytidine
Leukocytes
Breast Neoplasms
Confidence Intervals
DNA
Electrospray Ionization Mass Spectrometry
Tandem Mass Spectrometry
Liquid Chromatography
Case-Control Studies
Odds Ratio

Keywords

  • %5mdC
  • Breast cancer
  • Cohort
  • Global DNA methylation
  • White blood cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, colorectal, and Ovarian cancer screening trial (PLCO). / Sturgeon, Susan R.; Pilsner, J. Richard; Arcaro, Kathleen F.; Ikuma, Kaoru; Wu, Haotian; Kim, Soon Mi; Chopra-Tandon, Nayha; Karpf, Adam R; Ziegler, Regina G.; Schairer, Catherine; Balasubramanian, Raji; Reckhow, David A.

In: Breast Cancer Research, Vol. 19, No. 1, 94, 18.08.2017.

Research output: Contribution to journalArticle

Sturgeon, SR, Pilsner, JR, Arcaro, KF, Ikuma, K, Wu, H, Kim, SM, Chopra-Tandon, N, Karpf, AR, Ziegler, RG, Schairer, C, Balasubramanian, R & Reckhow, DA 2017, 'White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, colorectal, and Ovarian cancer screening trial (PLCO)', Breast Cancer Research, vol. 19, no. 1, 94. https://doi.org/10.1186/s13058-017-0886-6
Sturgeon, Susan R. ; Pilsner, J. Richard ; Arcaro, Kathleen F. ; Ikuma, Kaoru ; Wu, Haotian ; Kim, Soon Mi ; Chopra-Tandon, Nayha ; Karpf, Adam R ; Ziegler, Regina G. ; Schairer, Catherine ; Balasubramanian, Raji ; Reckhow, David A. / White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, colorectal, and Ovarian cancer screening trial (PLCO). In: Breast Cancer Research. 2017 ; Vol. 19, No. 1.
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abstract = "Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2' deoxycytidine [5-mdC] to 2'-deoxyguanine [dG], assuming [dG]=[5-mdC]+[2'-deoxycytidine [dC]] ({\%}5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results: Odds ratio (OR) estimates and 95{\%} confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95{\%} CI, 0.6-1.3), 0.88 (95{\%} CI, 0.6-1.3), and 0.84 (95{\%} CI, 0.6-1.2) for women in the highest compared to lowest quartile levels of {\%}5md-C (p for trend=.39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion: These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.",
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AU - Pilsner, J. Richard

AU - Arcaro, Kathleen F.

AU - Ikuma, Kaoru

AU - Wu, Haotian

AU - Kim, Soon Mi

AU - Chopra-Tandon, Nayha

AU - Karpf, Adam R

AU - Ziegler, Regina G.

AU - Schairer, Catherine

AU - Balasubramanian, Raji

AU - Reckhow, David A.

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N2 - Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2' deoxycytidine [5-mdC] to 2'-deoxyguanine [dG], assuming [dG]=[5-mdC]+[2'-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results: Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6-1.3), 0.88 (95% CI, 0.6-1.3), and 0.84 (95% CI, 0.6-1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend=.39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion: These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.

AB - Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2' deoxycytidine [5-mdC] to 2'-deoxyguanine [dG], assuming [dG]=[5-mdC]+[2'-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. Results: Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6-1.3), 0.88 (95% CI, 0.6-1.3), and 0.84 (95% CI, 0.6-1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend=.39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. Discussion: These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.

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