PMID- 32614429
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20221207
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 41
IP  - 9
DP  - 2020 Sep 24
TI  - Genetic variants in the human leukocyte antigen region and survival of Chinese 
      patients with non-small cell lung carcinoma.
PG  - 1203-1212
LID - 10.1093/carcin/bgaa066 [doi]
AB  - Human leukocyte antigen (HLA) is highly polymorphic, driving antigen 
      presentation, complement cascade and leukocyte maturation against cancer cells. 
      Therefore, we extracted genotyping data in the HLA region from an ongoing Chinese 
      genome-wide association study of non-small cell lung cancer (NSCLC). Using deep 
      sequencing data of 10 689 healthy Han Chinese, we imputed for untyped genetic 
      variants in the HLA region, followed by a two-stage survival analysis of 1531 
      NSCLC patients. In the discovery stage of 758 patients, we identified 301 out of 
      15 138 single-nucleotide polymorphisms to be independently associated with 
      overall survival [P < 0.05 and Bayesian false-discovery probability < 0.8]. In 
      further validation of another 773 patients, we confirmed chromosome 6p21, 
      rs241424 (located at intron 3 of TAP2) and rs6457642 as two independent survival 
      predictors. In the combined analysis of 1531 NSCLC patients, rs241424 G>A and 
      rs6457642 C>T were associated with a hazards ratio of 1.26 [95% confidence 
      interval (CI) = 1.14-1.40 and P = 4.04 x 10-6] and 0.76 (95% CI = 0.66-0.87 and P 
      = 1.16 x 10-4), respectively. The analysis of publically available 
      ChIP-sequencing and Hi-C data found that the rs241424 locus was involved in 
      potential cis-regulatory element by a long-range interaction with the HLA-DQA1 
      promoter. Additional expression quantitative trait loci analysis showed that the 
      rs241424 G>A change decreased HLA-DQA1 mRNA expression. Furthermore, expression 
      levels of HLA-DQA1 were lower in lung cancer tissues than in adjacent normal 
      tissues, and the lower expression was associated with a worse prognosis for 
      patients with lung adenocarcinoma. Collectively, HLA genetic variants may 
      modulate OS of NSCLC patients, possibly via a mechanism of long-range promoter 
      interaction regulating HLA-DQA1 expression.
CI  - (c) The Author(s) 2020. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Cheng, Lei
AU  - Cheng L
AD  - Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan 
      University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
AD  - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Liu, Qi
AU  - Liu Q
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Wang, Mengyun
AU  - Wang M
AD  - Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan 
      University Shanghai Cancer Center, Shanghai, China.
FAU - Gu, Yanzi
AU  - Gu Y
AD  - Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
FAU - Wang, Jialei
AU  - Wang J
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Wei, Qingyi
AU  - Wei Q
AD  - Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan 
      University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Population Health Sciences, Duke University School of Medicine, 
      Durham, NC, USA.
AD  - Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
FAU - Zhang, Ruoxin
AU  - Zhang R
AD  - Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan 
      University Shanghai Cancer Center, Shanghai, China.
AD  - School of Public Health, Fudan University, Shanghai, China.
AD  - Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Asian People/*genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*mortality/pathology/therapy
MH  - Case-Control Studies
MH  - Combined Modality Therapy
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Lung Neoplasms/genetics/*mortality/pathology/therapy
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Quantitative Trait Loci
MH  - Retrospective Studies
MH  - Survival Rate
EDAT- 2020/07/03 06:00
MHDA- 2021/05/27 06:00
CRDT- 2020/07/03 06:00
PHST- 2020/04/06 00:00 [received]
PHST- 2020/06/13 00:00 [revised]
PHST- 2020/06/23 00:00 [accepted]
PHST- 2020/07/03 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/07/03 06:00 [entrez]
AID - 5866472 [pii]
AID - 10.1093/carcin/bgaa066 [doi]
PST - ppublish
SO  - Carcinogenesis. 2020 Sep 24;41(9):1203-1212. doi: 10.1093/carcin/bgaa066.