White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-017-0886-6 |
| _version_ | 1819181106816090112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Susan R. Sturgeon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T22:24:58Z |
| format | Article |
| id | doaj.art-5c1f5ef399d04cd88c27d50766796280 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-22T22:24:58Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-5c1f5ef399d04cd88c27d507667962802022-12-21T18:10:35ZengBMCBreast Cancer Research1465-542X2017-08-0119111110.1186/s13058-017-0886-6White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)Susan R. Sturgeon0J. Richard Pilsner1Kathleen F. Arcaro2Kaoru Ikuma3Haotian Wu4Soon-Mi Kim5Nayha Chopra-Tandon6Adam R. Karpf7Regina G. Ziegler8Catherine Schairer9Raji Balasubramanian10David A. Reckhow11Department of Biostatistics and Epidemiology, University of Massachusetts-AmherstDepartment of Environmental Health Sciences, University of MassachusettsDepartment of Veterinary and Animal Sciences, University of MassachusettsDepartment of Civil and Environmental Engineering, University of MassachusettsDepartment of Environmental Health Sciences, University of MassachusettsDepartment of Civil and Environmental Engineering, University of MassachusettsDepartment of Biostatistics and Epidemiology, University of Massachusetts-AmherstEppley Institute and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical CenterEpidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer instituteEpidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer instituteDepartment of Biostatistics and Epidemiology, University of Massachusetts-AmherstDepartment of Civil and Environmental Engineering, University of MassachusettsAbstract 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.http://link.springer.com/article/10.1186/s13058-017-0886-6Breast cancerWhite blood cellsGlobal DNA methylation%5mdCCohort |
| spellingShingle | 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 White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Breast Cancer Research Breast cancer White blood cells Global DNA methylation %5mdC Cohort |
| title | White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) |
| title_full | White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) |
| title_fullStr | White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) |
| title_full_unstemmed | White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) |
| title_short | White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) |
| title_sort | white blood cell dna methylation and risk of breast cancer in the prostate lung colorectal and ovarian cancer screening trial plco |
| topic | Breast cancer White blood cells Global DNA methylation %5mdC Cohort |
| url | http://link.springer.com/article/10.1186/s13058-017-0886-6 |
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