PMID- 30099827
OWN - NLM
STAT- MEDLINE
DCOM- 20181012
LR  - 20210109
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 109
IP  - 10
DP  - 2018 Oct
TI  - Fatty pancreas: A possible risk factor for pancreatic cancer in animals and 
      humans.
PG  - 3013-3023
LID - 10.1111/cas.13766 [doi]
AB  - Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic 
      cancer risk, but the mechanisms of pancreatic cancer development caused by these 
      factors are not clearly understood. Syrian golden hamsters are susceptible to 
      N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis. Aging, 
      BOP treatment and/or a high-fat diet cause severe and scattered fatty 
      infiltration (FI) of the pancreas with abnormal adipokine production and promote 
      pancreatic ductal adenocarcinoma (PDAC) development. The KK-A(y) mouse, a T2DM 
      model, also develops severe and scattered FI of the pancreas. Treatment with BOP 
      induced significantly higher cell proliferation in the pancreatic ducts of 
      KK-A(y) mice, but not in those of ICR and C57BL/6J mice, both of which are 
      characterized by an absence of scattered FI. Thus, we hypothesized that severely 
      scattered FI may be involved in the susceptibility to PDAC development. Indeed, 
      severe pancreatic FI, or fatty pancreas, is observed in humans and is associated 
      with age, body mass index (BMI) and DM, which are risk factors for pancreatic 
      cancer. We analyzed the degree of FI in the non-cancerous parts of PDAC and 
      non-PDAC patients who had undergone pancreatoduodenectomy by histopathology and 
      demonstrated that the degree of pancreatic FI in PDAC cases is significantly 
      higher than that in non-PDAC controls. Moreover, the association with PDAC is 
      positive, even after adjusting for BMI and the prevalence of DM. Accumulating 
      evidence suggests that pancreatic FI is involved in PDAC development in animals 
      and humans, and further investigations to clarify the genetic and environmental 
      factors that cause pancreatic FI are warranted.
CI  - (c) 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Takahashi, Mami
AU  - Takahashi M
AUID- ORCID: 0000-0001-5062-811X
AD  - Central Animal Division, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Hori, Mika
AU  - Hori M
AD  - Department of Molecular Innovation in Lipidology, National Cerebral and 
      Cardiovascular Center Research Institute, Osaka, Japan.
FAU - Ishigamori, Rikako
AU  - Ishigamori R
AD  - Central Animal Division, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Mutoh, Michihiro
AU  - Mutoh M
AUID- ORCID: 0000-0003-2054-7655
AD  - Epidemiology and Prevention Division, Research Center for Cancer Prevention and 
      Screening, National Cancer Center, Tokyo, Japan.
FAU - Imai, Toshio
AU  - Imai T
AD  - Central Animal Division, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Nakagama, Hitoshi
AU  - Nakagama H
AD  - National Cancer Center, Tokyo, Japan.
LA  - eng
GR  - 15K14393/Grant-in-Aid for Scientific Research from the Japan Society for the 
      Promotion of Science/
GR  - 18K07081/Grant-in-Aid for Scientific Research from the Japan Society for the 
      Promotion of Science/
GR  - 25290049/Grant-in-Aid for Scientific Research from the Japan Society for the 
      Promotion of Science/
GR  - Research Grant of the Princess Takamatsu Cancer Research Fund/
GR  - grant of the Third-Term Comprehensive 10-Year Strategy for Cancer Control from 
      the Ministry of Health, Labor, and Welfare of Japan/
GR  - Grants-in-Aid from the Foundation for Promotion of Cancer Research and the 
      Pancreas Research Foundation of Japan/
GR  - 21-2-1/Grants-in-Aid for Cancer Research from the Ministry of Health, Labour, and 
      Welfare of Japan and Management Expenses Grants from the Government to the 
      National Cancer Center/
GR  - National Cancer Center Research Core Facility/
PT  - Journal Article
PT  - Review
DEP - 20180905
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Carcinogens)
SB  - IM
MH  - Adipose Tissue/*pathology
MH  - Animals
MH  - Carcinogens/toxicity
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Diet, High-Fat/adverse effects
MH  - Disease Models, Animal
MH  - Humans
MH  - Obesity/*complications
MH  - Pancreas/*pathology
MH  - Pancreatic Neoplasms/*etiology/pathology
MH  - Risk Factors
PMC - PMC6172058
OTO - NOTNLM
OT  - cancer susceptibility
OT  - fatty infiltration
OT  - obesity
OT  - pancreatic cancer
OT  - type 2 diabetes mellitus
EDAT- 2018/08/14 06:00
MHDA- 2018/10/13 06:00
PMCR- 2018/10/01
CRDT- 2018/08/13 06:00
PHST- 2018/05/01 00:00 [received]
PHST- 2018/08/01 00:00 [revised]
PHST- 2018/08/04 00:00 [accepted]
PHST- 2018/08/14 06:00 [pubmed]
PHST- 2018/10/13 06:00 [medline]
PHST- 2018/08/13 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - CAS13766 [pii]
AID - 10.1111/cas.13766 [doi]
PST - ppublish
SO  - Cancer Sci. 2018 Oct;109(10):3013-3023. doi: 10.1111/cas.13766. Epub 2018 Sep 5.