PMID- 32907841
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20240216
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 80
IP  - 20
DP  - 2020 Oct 15
TI  - A Transcriptome-Wide Association Study Identifies Candidate Susceptibility Genes 
      for Pancreatic Cancer Risk.
PG  - 4346-4354
LID - 10.1158/0008-5472.CAN-20-1353 [doi]
AB  - Pancreatic cancer is among the most well-characterized cancer types, yet a large 
      proportion of the heritability of pancreatic cancer risk remains unclear. Here, 
      we performed a large transcriptome-wide association study to systematically 
      investigate associations between genetically predicted gene expression in normal 
      pancreas tissue and pancreatic cancer risk. Using data from 305 subjects of 
      mostly European descent in the Genotype-Tissue Expression Project, we built 
      comprehensive genetic models to predict normal pancreas tissue gene expression, 
      modifying the UTMOST (unified test for molecular signatures). These prediction 
      models were applied to the genetic data of 8,275 pancreatic cancer cases and 
      6,723 controls of European ancestry. Thirteen genes showed an association of 
      genetically predicted expression with pancreatic cancer risk at an FDR </= 0.05, 
      including seven previously reported genes (INHBA, SMC2, ABO, PDX1, RCCD1, CFDP1, 
      and PGAP3) and six novel genes not yet reported for pancreatic cancer risk [6q27: 
      SFT2D1 OR (95% confidence interval (CI), 1.54 (1.25-1.89); 13q12.13: MTMR6 OR 
      (95% CI), 0.78 (0.70-0.88); 14q24.3: ACOT2 OR (95% CI), 1.35 (1.17-1.56); 17q12: 
      STARD3 OR (95% CI), 6.49 (2.96-14.27); 17q21.1: GSDMB OR (95% CI), 1.94 
      (1.45-2.58); and 20p13: ADAM33 OR (95% CI): 1.41 (1.20-1.66)]. The associations 
      for 10 of these genes (SFT2D1, MTMR6, ACOT2, STARD3, GSDMB, ADAM33, SMC2, RCCD1, 
      CFDP1, and PGAP3) remained statistically significant even after adjusting for 
      risk SNPs identified in previous genome-wide association study. Collectively, 
      this analysis identified novel candidate susceptibility genes for pancreatic 
      cancer that warrant further investigation. SIGNIFICANCE: A transcriptome-wide 
      association analysis identified seven previously reported and six novel candidate 
      susceptibility genes for pancreatic cancer risk.
CI  - (c)2020 American Association for Cancer Research.
FAU - Liu, Duo
AU  - Liu D
AD  - Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, 
      Heilongjiang, P.R. China.
AD  - Division of Cancer Epidemiology, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, 
      Hawaii.
FAU - Zhou, Dan
AU  - Zhou D
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
FAU - Sun, Yanfa
AU  - Sun Y
AD  - Division of Cancer Epidemiology, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, 
      Hawaii.
AD  - College of Life Science, Longyan University, Longyan, Fujian, P.R. China.
AD  - Fujian Provincial Key Laboratory for the Prevention and Control of Animal 
      Infectious Diseases and Biotechnology, Longyan, Fujian, P.R. China.
AD  - Key Laboratory of Preventive Veterinary Medicine and Biotechnology (Longyan 
      University), Fujian Province University, Longyan, Fujian, P.R. China.
FAU - Zhu, Jingjing
AU  - Zhu J
AD  - Division of Cancer Epidemiology, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, 
      Hawaii.
FAU - Ghoneim, Dalia
AU  - Ghoneim D
AD  - Division of Cancer Epidemiology, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, 
      Hawaii.
FAU - Wu, Chong
AU  - Wu C
AD  - Department of Statistics, Florida State University, Tallahassee, Florida.
FAU - Yao, Qizhi
AU  - Yao Q
AUID- ORCID: 0000-0002-2267-0588
AD  - Division of Surgical Oncology, Michael E. DeBakey Department of Surgery, Baylor 
      College of Medicine, Houston, Texas.
AD  - Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. 
      DeBakey VA Medical Center, Houston, Texas.
FAU - Gamazon, Eric R
AU  - Gamazon ER
AUID- ORCID: 0000-0003-4204-8734
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
AD  - Clare Hall, University of Cambridge, Cambridge, United Kingdom.
AD  - MRC Epidemiology Unit, School of Clinical Medicine, University of Cambridge, 
      Cambridge, United Kingdom.
FAU - Cox, Nancy J
AU  - Cox NJ
AD  - Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
FAU - Wu, Lang
AU  - Wu L
AD  - Division of Cancer Epidemiology, Population Sciences in the Pacific Program, 
      University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, 
      Hawaii. lwu@cc.hawaii.edu.
LA  - eng
GR  - R01 HG011138/HG/NHGRI NIH HHS/United States
GR  - R00 CA218892/CA/NCI NIH HHS/United States
GR  - HHSN268201100011I/HL/NHLBI NIH HHS/United States
GR  - HHSN268201100011C/HL/NHLBI NIH HHS/United States
GR  - I01 CX001822/CX/CSRD VA/United States
GR  - K07 CA140790/CA/NCI NIH HHS/United States
GR  - R01 CA154823/CA/NCI NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - U01 HG009086/HG/NHGRI NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - R35 HG010718/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200909
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Age Factors
MH  - Case-Control Studies
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - Models, Genetic
MH  - Pancreatic Neoplasms/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - White People/genetics
PMC - PMC7572664
MID - NIHMS1622598
COIS- Competing financial interests Eric Gamazon receives an honorarium from the 
      journal Circulation Research of the American Heart Association as a member of the 
      Editorial Board. There is no potential conflict of interests for other authors.
EDAT- 2020/09/11 06:00
MHDA- 2021/02/11 06:00
PMCR- 2021/04/15
CRDT- 2020/09/10 05:28
PHST- 2020/04/21 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/08/14 00:00 [accepted]
PHST- 2020/09/11 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PHST- 2020/09/10 05:28 [entrez]
PHST- 2021/04/15 00:00 [pmc-release]
AID - 0008-5472.CAN-20-1353 [pii]
AID - 10.1158/0008-5472.CAN-20-1353 [doi]
PST - ppublish
SO  - Cancer Res. 2020 Oct 15;80(20):4346-4354. doi: 10.1158/0008-5472.CAN-20-1353. 
      Epub 2020 Sep 9.