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Integrating Genome and Methylome Data to Identify Candidate DNA Methylation Biomarkers for Pancreatic Cancer Risk.
Zhu, Jingjing; Yang, Yaohua; Kisiel, John B; Mahoney, Douglas W; Michaud, Dominique S; Guo, Xingyi; Taylor, William R; Shu, Xiao-Ou; Shu, Xiang; Liu, Duo; Li, Bingshan; Tao, Ran; Cai, Qiuyin; Zheng, Wei; Long, Jirong; Wu, Lang.
Afiliação
  • Zhu J; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
  • Yang Y; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Kisiel JB; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Mahoney DW; Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
  • Michaud DS; Department of Public Health and Community Medicine, Tufts University Medical School, Boston, Massachusetts.
  • Guo X; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Taylor WR; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Shu X; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Liu D; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
  • Li B; Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China.
  • Tao R; Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, Tennessee.
  • Cai Q; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Zheng W; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Long J; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Wu L; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Epidemiol Biomarkers Prev ; 30(11): 2079-2087, 2021 11.
Article em En | MEDLINE | ID: mdl-34497089
ABSTRACT

BACKGROUND:

The role of methylation in pancreatic cancer risk remains unclear. We integrated genome and methylome data to identify CpG sites (CpG) with the genetically predicted methylation to be associated with pancreatic cancer risk. We also studied gene expression to understand the identified associations.

METHODS:

Using genetic data and white blood cell methylation data from 1,595 subjects of European descent, we built genetic models to predict DNA methylation levels. After internal and external validation, we applied prediction models with satisfactory performance to the genetic data of 8,280 pancreatic cancer cases and 6,728 controls of European ancestry to investigate the associations of predicted methylation with pancreatic cancer risk. For associated CpGs, we compared their measured levels in pancreatic tumor versus benign tissue.

RESULTS:

We identified 45 CpGs at nine loci showing an association with pancreatic cancer risk, including 15 CpGs showing an association independent from identified risk variants. We observed significant correlations between predicted methylation of 16 of the 45 CpGs and predicted expression of eight adjacent genes, of which six genes showed associations with pancreatic cancer risk. Of the 45 CpGs, we were able to compare measured methylation of 16 in pancreatic tumor versus benign pancreatic tissue. Of them, six showed differentiated methylation.

CONCLUSIONS:

We identified methylation biomarker candidates associated with pancreatic cancer using genetic instruments and added additional insights into the role of methylation in regulating gene expression in pancreatic cancer development. IMPACT A comprehensive study using genetic instruments identifies 45 CpG sites at nine genomic loci for pancreatic cancer risk.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Metilação de DNA Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Metilação de DNA Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Ano de publicação: 2021 Tipo de documento: Article