| Περίληψη: | Lifestyle factors, such as food choices and exposure to chemicals, can alter DNAmethylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea have been suggested to play an important role inmodulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogenmetabolism. Thesemechanismsmay bemediated by changes in DNA methylation. To investigate if DNAmethylation in blood is associated with coffee and tea consumption, we performed a genome-wide DNAmethylation study for coffee and tea consumption in four European cohorts (N=3,096). DNAmethylation wasmeasured fromwhole blood at 421,695 CpG sites distributed throughout the genome and analysed inmen and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed. After adjusting formultiple testing, themeta-analysis revealed that two individual CpG-sites,mapping to DNAJC16 and TTC17, were differentiallymethylated in relation to tea consumption in women. No individual sites were associated withmen or with the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentiallymethylated in relation to tea consumption in women. These regions contained genes known to interact with estradiolmetabolismand cancer. No significant regions were found in the sex-combined andmale-only analysis for either tea or coffee consumption. |
| Σημειώσεις: | 01947, LSHG-CT-2006-01947; 259679; National Institutes of Health, NIH: AG042190, HL067914; Åke Wiberg Stiftelse; Breast Cancer Now, BCN; Imperial Experimental Cancer Medicine Centre, ECMC; Göran Gustafssons Stiftelser: K2007-66X-20270-01-3; National Institute for Health Research, NIHR; Cancer Research UK, CRUK: A13086; European Commission, EC: 226756; Stiftelsen för Strategisk Forskning, SSF; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO: 91617128; Svenska Sällskapet för Medicinsk Forskning, SSMF; Vetenskapsrådet, VR: 70374401, 80576801; Medicinska Forskningsrådet, MFR: 2011-2354; Kjell och Märta Beijers Stiftelse; Uppsala Universitet; Science for Life Laboratory, SciLifeLab.
Uppsala University, Uppsala University Hospital, Science for Life Laboratory (SciLifeLab) - Uppsala and the Swedish Research Council (Contracts 80576801 and 70374401), Swedish Medical Research Council (Project Number 2011-2354 and K2007-66X-20270-01-3) and the Göran Gustafssons Foundation, Foundation for Strategic Research (SSF), European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947), Swedish Society for Medical Research (SSMF), Kjell och Ma€rta Beijers Foundation, The Marcus Borgström Foundation, Åke Wiberg foundation and the Vleugels Foundation, Breast Cancer Now, CRUK programme grant A13086, the Imperial College Experimental Cancer Medicine Centre (ECMC), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), U.S. National Institutes of Health, European Union’s Seventh Framework Program IDEAL (259679) , NWO VENI grant (91617128), and European Union (Grant number 226756). W.E.E and Å.J planned the study and interpreted the data. W.E.E, Å.J, E.P, J.M.F, E.L and E.W.T analyzed the data. All authors wrote and critically reviewed the manuscript for important intellectual content. We are grateful to all the participants from the community for their interest and willingness to contribute to this study. Illumina genotyping, and DNA methylation analyses was performed by the SNP & SEQ Technology Platform in Uppsala, which is supported by Uppsala University, Uppsala University Hospital, Science for Life Laboratory (SciLifeLab) - Uppsala and the Swedish Research Council (Contracts 80576801 and 70374401). The computations were performed on resources provided by SNIC through the Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects b2011203, p2012153 and b2013110. We are grateful to the participants of the Dutch Hunger Winter Families study and the staff of TNO Quality of Life for contact tracing. At the Leiden University Medical Center we wish to acknowledge the staff of the department of Gerontology and Geriatrics Study Center for the physical examinations and the Central Clinical Chemical Laboratory for extracting DNA. The DNA Methylation study in NSPHS has been funded by the Swedish Medical Research Council (Project Number 2011-2354) and the Göran Gustafssons Foundation. The NSPHS study was funded by the Swedish Medical Research Council (Project Number K2007-66X-20270-01-3) and the Foundation for Strategic Research (SSF). NSPHS as part of EUROSPAN (European Special Populations Research Network) was also supported by European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947). This work has also been supported by the Swedish Society for Medical Research (SSMF), the Kjell och Ma€rta Beijers Foundation, The Marcus Borgström Foundation, the Åke Wiberg foundation and the Vleugels Foundation. JMF acknowledges funding from Breast Cancer Now, CRUK programme grant A13086, the Imperial College Experimental Cancer Medicine Centre (ECMC) and the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC). The Hunger Winter Families Study was supported by the U.S. National Institutes of Health [AG042190 to LHL and BTH, HL067914 to LHL] and the European Union’s Seventh Framework Program IDEAL (259679) and EWT was supported by a NWO VENI grant (91617128). The EnviroGenomarkers project was partly funded by the European Union (Grant number 226756). |
