
PMID- 32430337
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20211124
IS  - 1538-7755 (Electronic)
IS  - 1055-9965 (Print)
IS  - 1055-9965 (Linking)
VI  - 29
IP  - 8
DP  - 2020 Aug
TI  - DNA Methylation-Derived Immune Cell Profiles, CpG Markers of Inflammation, and 
      Pancreatic Cancer Risk.
PG  - 1577-1585
LID - 10.1158/1055-9965.EPI-20-0378 [doi]
AB  - BACKGROUND: Pancreatic cancer is projected to become the second most common cause 
      of cancer-related death over the next 5 years. Because inflammation is thought to 
      be a common trajectory for disease initiation, we sought to prospectively 
      characterize immune profiles using DNA methylation markers and examine DNA 
      methylation levels previously linked to inflammation biomarkers to evaluate 
      whether these immune markers play a key role in pancreatic cancer. METHODS: In a 
      nested case-control study pooling three U.S. prospective cohort studies, DNA 
      methylation was measured in prediagnostic leukocytes of incident pancreatic 
      cancer cases and matched controls using the Illumina MethylationEPIC array. 
      Differentially methylated regions were used to predict immune cell types, and 
      CpGs previously associated with inflammatory biomarkers were selected for the 
      analysis. DNA methylation data from a retrospective case-control study conducted 
      in Spain (PanGenEU) was used for independent replication. RESULTS: Immune cell 
      proportions and ratio of cell proportions were not associated with pancreatic 
      cancer risk in the nested case-control study. Methylation extent of CpGs residing 
      in or near gene MNDA was significantly associated with pancreatic cancer risk in 
      the nested case-control study and replicated in PanGenEU. Methylation level of a 
      promoter CpG of gene PIM-1 was associated with survival in both studies. 
      CONCLUSIONS: Using a targeted approach, we identified several CpGs that may play 
      a role in pancreatic carcinogenesis in two large, independent studies with 
      distinct study designs. IMPACT: These findings could provide insight into 
      critical pathways that may help identify new markers of early disease and 
      survival.
CI  - (c)2020 American Association for Cancer Research.
FAU - Michaud, Dominique S
AU  - Michaud DS
AD  - Department of Public Health & Community Medicine, Tufts University School of 
      Medicine, Tufts University, Boston, Massachusetts. Dominique.Michaud@tufts.edu.
AD  - Department of Epidemiology, Brown University, Providence, Rhode Island.
FAU - Ruan, Mengyuan
AU  - Ruan M
AUID- ORCID: 0000-0001-7555-8963
AD  - Department of Public Health & Community Medicine, Tufts University School of 
      Medicine, Tufts University, Boston, Massachusetts.
FAU - Koestler, Devin C
AU  - Koestler DC
AD  - Department of Biostatistics & Data Science, University of Kansas Medical Center, 
      Kansas City, Kansas.
AD  - University of Kansas Cancer Center, University of Kansas Medical Center, Kansas 
      City, Kansas.
FAU - Alonso, Lola
AU  - Alonso L
AUID- ORCID: 0000-0002-3493-718X
AD  - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre 
      (CNIO) and CIBERONC, Madrid, Spain.
FAU - Molina-Montes, Esther
AU  - Molina-Montes E
AD  - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre 
      (CNIO) and CIBERONC, Madrid, Spain.
FAU - Pei, Dong
AU  - Pei D
AD  - Department of Biostatistics & Data Science, University of Kansas Medical Center, 
      Kansas City, Kansas.
AD  - University of Kansas Cancer Center, University of Kansas Medical Center, Kansas 
      City, Kansas.
FAU - Marsit, Carmen J
AU  - Marsit CJ
AUID- ORCID: 0000-0003-4566-150X
AD  - Department of Environmental Health and Department of Epidemiology, Rollins School 
      of Public Health, Emory University, Atlanta, Georgia.
FAU - De Vivo, Immaculata
AU  - De Vivo I
AD  - Channing Division of Network Medicine, Department of Medicine, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Malats, Nuria
AU  - Malats N
AD  - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre 
      (CNIO) and CIBERONC, Madrid, Spain.
FAU - Kelsey, Karl T
AU  - Kelsey KT
AD  - Department of Epidemiology, Brown University, Providence, Rhode Island.
AD  - Department of Pathology and Laboratory Medicine, Brown University, Providence, 
      Rhode Island.
LA  - eng
GR  - P20 GM103418/GM/NIGMS NIH HHS/United States
GR  - P20 GM130423/GM/NIGMS NIH HHS/United States
GR  - R01 CA207110/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200519
PL  - United States
TA  - Cancer Epidemiol Biomarkers Prev
JT  - Cancer epidemiology, biomarkers & prevention : a publication of the American 
      Association for Cancer Research, cosponsored by the American Society of 
      Preventive Oncology
JID - 9200608
RN  - 0 (Biomarkers)
SB  - IM
MH  - Biomarkers/*metabolism
MH  - Case-Control Studies
MH  - DNA Methylation/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/*genetics/mortality
MH  - Risk Factors
MH  - Survival Analysis
PMC - PMC7415654
MID - NIHMS1596759
COIS- Conflict of Interest The authors have no conflicts of interests.
EDAT- 2020/05/21 06:00
MHDA- 2021/11/25 06:00
PMCR- 2021/02/01
CRDT- 2020/05/21 06:00
PHST- 2020/03/10 00:00 [received]
PHST- 2020/04/09 00:00 [revised]
PHST- 2020/05/13 00:00 [accepted]
PHST- 2020/05/21 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2020/05/21 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 1055-9965.EPI-20-0378 [pii]
AID - 10.1158/1055-9965.EPI-20-0378 [doi]
PST - ppublish
SO  - Cancer Epidemiol Biomarkers Prev. 2020 Aug;29(8):1577-1585. doi: 
      10.1158/1055-9965.EPI-20-0378. Epub 2020 May 19.
