Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies.
Background: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in l...
| Publicado en: | Breast Cancer Research Vol. 21; no. 1 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
5/17/2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=136503576&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 136503576 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 5/17/2019 vid: 21 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 136503576 136503576 NLM31101124 136503576 10.1186/s13058-019-1145-9 NLM31101124 136503576 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies. aug: au: Bodelon, Clara Ambatipudi, Srikant Dugué, Pierre-Antoine Johansson, Annelie Sampson, Joshua N. Hicks, Belynda Karlins, Eric Hutchinson, Amy Cuenin, Cyrille Chajès, Veronique Southey, Melissa C. Romieu, Isabelle Giles, Graham G. English, Dallas Polidoro, Silvia Assumma, Manuela Baglietto, Laura Vineis, Paolo Severi, Gianluca Herceg, Zdenko affil: Divison of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA sug: subj: DNA Breast Neoplasms DNA Methylation Genes Risk Factors Middle Age Odds Ratio Case Control Studies Risk Assessment Female Prospective Studies Gene Expression Profiling Human Breast Neoplasms Blood Validation Studies Comparative Studies Evaluation Research Multicenter Studies Ferrans and Powers Quality of Life Index Psychological Tests Middle Aged: 45-64 years Female ab: Background: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date.Methods: We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis (< 50, ≥ 50), estrogen receptor (ER) status (+/-), and time since blood collection (< 5, 5-10, > 10 years). The false discovery rate (q value) was used to account for multiple testing.Results: The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98).Conclusions: Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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