PMID- 31001878
OWN - NLM
STAT- MEDLINE
DCOM- 20191107
LR  - 20191107
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 58
IP  - 7
DP  - 2019 Jul
TI  - Genome-wide expression profiling-based copy number variations and colorectal 
      cancer risk in Chinese.
PG  - 1324-1333
LID - 10.1002/mc.23015 [doi]
AB  - Genetic factors play important roles in colorectal carcinogenesis. This study was 
      aimed to evaluate the effects of gene expression-related copy number variations 
      (CNVs) on the risk of colorectal cancer in Chinese. Expression Quantitative Trait 
      Locus (eQTL) mapping was conducted to explore the most regulatable gene 
      expressions by CNVs among the whole genome based on publicly available data. Then 
      a case-control study was performed to evaluate the associations between copy 
      numbers of the most regulatable genes and colorectal cancer. The influence of the 
      target CNVs on the expression of corresponding gene and protein was verified in 
      colorectal tissue, and the biological effects of these CNVs on cell-cycle arrest 
      and apoptosis of colon cancer cell lines were further detected. The eQTL revealed 
      the most significant association between CNV of HM3_CNP_342 and gene expressions 
      of human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 among the whole genome. The 
      later case-control study found that amplified HLA-DQB1 was inversely associated 
      with colorectal cancer risk (odds ratio = 0.73; 95% confidence interval: 
      0.58-0.93), especially among those with a family history of cancer. The positive 
      association between amplified HLA-DQB1 and upregulation of gene and protein was 
      validated in colorectal tissue. In addition, overexpression of HLA-DQB1 in 
      dendritic cells promoted cell-cycle arrest and apoptosis of cocultured SW480 and 
      HCT116 cell lines, and vice versa. Our study suggests that the amplified copy 
      number of HLA-DQB1 is associated with lower risk of colorectal cancer and able to 
      induce the apoptosis of colon cancer cells, which implies the potential of HLA 
      class II in cancer predisposition and immunotherapy.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Wang, Ke
AU  - Wang K
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
AD  - Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, China.
FAU - Yu, Xingchen
AU  - Yu X
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Jiang, Hongwei
AU  - Jiang H
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Huang, Jiao
AU  - Huang J
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Wang, Huanzhuo
AU  - Wang H
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Jiang, Hongyu
AU  - Jiang H
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Wei, Sheng
AU  - Wei S
AUID- ORCID: 0000-0001-6888-6301
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
FAU - Liu, Li
AU  - Liu L
AUID- ORCID: 0000-0001-7455-1735
AD  - Department of Epidemiology and Biostatistics, Ministry of Education Key 
      Laboratory of Environment and Health, School of Public Health, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190418
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Apoptosis/genetics
MH  - Case-Control Studies
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Line, Tumor
MH  - China
MH  - Colonic Neoplasms/*genetics
MH  - DNA Copy Number Variations/*genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - HCT116 Cells
MH  - HEK293 Cells
MH  - HLA-DQ alpha-Chains/*genetics
MH  - HLA-DQ beta-Chains/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Quantitative Trait Loci/genetics
OTO - NOTNLM
OT  - apoptosis
OT  - colorectal cancer
OT  - copy number variation
OT  - expression quantitative trait locus
OT  - human leukocyte antigen
EDAT- 2019/04/20 06:00
MHDA- 2019/11/08 06:00
CRDT- 2019/04/20 06:00
PHST- 2019/03/25 00:00 [received]
PHST- 2019/03/30 00:00 [accepted]
PHST- 2019/04/20 06:00 [pubmed]
PHST- 2019/11/08 06:00 [medline]
PHST- 2019/04/20 06:00 [entrez]
AID - 10.1002/mc.23015 [doi]
PST - ppublish
SO  - Mol Carcinog. 2019 Jul;58(7):1324-1333. doi: 10.1002/mc.23015. Epub 2019 Apr 18.