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Genetically Predict...
Genetically Predicted Levels of DNA Methylation Biomarkers and Breast Cancer Risk : Data From 228 951 Women of European Descent
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- Yang, Yaohua (författare)
- Vanderbilt University
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- Wu, Lang (författare)
- Vanderbilt University
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- Shu, Xiao Ou (författare)
- Vanderbilt University
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- Cai, Qiuyin (författare)
- Vanderbilt University
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- Shu, Xiang (författare)
- Vanderbilt University
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- Li, Bingshan (författare)
- Vanderbilt University
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- Guo, Xingyi (författare)
- Vanderbilt University
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- Ye, Fei (författare)
- Vanderbilt University
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- Michailidou, Kyriaki (författare)
- University of Cambridge
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- Bolla, Manjeet K. (författare)
- University of Cambridge
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- Wang, Qin (författare)
- University of Cambridge
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Dennis, Joe (författare)
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- Andrulis, Irene L. (författare)
- University of Cambridge,University of Toronto,Mount Sinai Hospital of University of Toronto
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- Brenner, Hermann (författare)
- German Cancer Research Centre
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- Chenevix-Trench, Georgia (författare)
- QIMR Berghofer Medical Research Institute
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- Campa, Daniele (författare)
- University of Pisa
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Castelao, Jose E. (författare)
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- Gago-Dominguez, Manuela (författare)
- University of California, San Diego,Complejo Hospitalario Universitario de Santiago
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- Dörk, Thilo (författare)
- Hannover Medical School
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- Hollestelle, Antoinette (författare)
- Erasmus University Medical Center
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- Lophatananon, Artitaya (författare)
- University of Manchester,University of Warwick
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- Muir, Kenneth (författare)
- University of Warwick,University of Manchester
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- Neuhausen, Susan L. (författare)
- Beckman Research Institute of City of Hope
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- Olsson, Håkan (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Sandler, Dale P. (författare)
- National Institute of Environmental Health Sciences
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- Simard, Jacques (författare)
- Laval University
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- Kraft, Peter (författare)
- Harvard University
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- Pharoah, Paul D.P. (författare)
- University of Cambridge
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- Easton, Douglas F. (författare)
- University of Cambridge
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- Zheng, Wei (författare)
- Vanderbilt University
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- Long, Jirong (författare)
- Vanderbilt University
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(creator_code:org_t)
- 2019-05-29
- 2020
- Engelska 10 s.
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 112:3, s. 295-304
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BACKGROUND: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. METHODS: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided. RESULTS: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. CONCLUSION: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (ämneskategori)
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Yang, Yaohua
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Wu, Lang
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Shu, Xiao Ou
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Cai, Qiuyin
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Shu, Xiang
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Li, Bingshan
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Guo, Xingyi
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Ye, Fei
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Michailidou, Kyr ...
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Bolla, Manjeet K ...
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Wang, Qin
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Dennis, Joe
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Andrulis, Irene ...
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Brenner, Hermann
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Chenevix-Trench, ...
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Campa, Daniele
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Castelao, Jose E ...
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Gago-Dominguez, ...
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Dörk, Thilo
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Hollestelle, Ant ...
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Lophatananon, Ar ...
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Muir, Kenneth
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Neuhausen, Susan ...
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Olsson, Håkan
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Sandler, Dale P.
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Simard, Jacques
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Kraft, Peter
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Pharoah, Paul D. ...
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Easton, Douglas ...
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Zheng, Wei
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Long, Jirong
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