PMID- 38107290
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231219
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 9
IP  - 12
DP  - 2023 Dec
TI  - Hypothyroidism reduces the risk of lung cancer through oxidative stress response 
      and the PI3K/Akt signaling pathway: An RNA-seq and Mendelian randomization study.
PG  - e22661
LID - 10.1016/j.heliyon.2023.e22661 [doi]
LID - e22661
AB  - Hypothyroidism has been suggested to play a role in tumor progression. However, 
      the causal association between hypothyroidism and lung cancer remains unknow. To 
      elucidate the potential association between hypothyroidism and lung cancer risk, 
      we employ a Mendelian randomization (MR) approach. MR was performed to analyze 
      pooled data from the International Lung Cancer Consortium (11,348 cases and 
      15,861 controls; European ancestry) to determine the causal relationship between 
      hypothyroidism and lung cancer. We used 36, 83, and 14 single nucleotide 
      polymorphisms as instrumental variables for hypothyroidism/myxoedema, 
      hypothyroidism, and exercise, respectively. We further investigated the 
      mechanisms involved in transcriptome analysis using data from The Cancer Genome 
      Atlas and Genotype-Tissue Expression database. We conducted an initial validation 
      of intermediary factor using a two-step MR analysis. Genetically predicted 
      hypothyroidism was significantly related to the risk of overall lung cancer, 
      specifically the risk of lung squamous cell cancer (LSCC) but not with the risk 
      of lung adenocarcinoma (LUAD) as assessed using the inverse-variance weighted 
      (IVM) method. A similar causal association was found between 
      hypothyroidism/myxoedema and the risk of lung cancer, LSCC, and LUAD. 
      Transcriptome analysis showed that genes associated with hypothyroidism, lung 
      cancer, and LSCC were enriched in the PI3K/Akt signaling pathway and oxidative 
      stress response. However, genes related to hypothyroidism and LUAD did not 
      exhibit enrichment in these pathways. Hypothyroidism was significantly associated 
      with strenuous sports or other exercises. Moreover, genetically predicted 
      exercise was significantly related to the risk of overall lung cancer, and LSCC, 
      but not LUAD. We detected no horizontal pleiotropy using the MR-PRESSO and MR 
      Egger regression intercept. Hypothyroidism was causally associated with a lower 
      risk of lung cancer, and these effects might be mediated by the oxidative stress 
      response and the PI3K/Akt signaling pathway. Therefore, our study suggests that 
      the potential factors and viable etiologies of hypothyroidism that contributed to 
      lung cancer risk deserve further investigation.
CI  - (c) 2023 The Authors.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
FAU - Zhi, Fei-Hang
AU  - Zhi FH
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
FAU - Zheng, Shao-Yi
AU  - Zheng SY
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
FAU - Yang, Hao-Shuai
AU  - Yang HS
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
FAU - Geng, Xi-Jie
AU  - Geng XJ
AD  - Operating Room and Anesthesia Centre, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China.
FAU - Luo, Hong-He
AU  - Luo HH
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
FAU - Feng, Yan-Fen
AU  - Feng YF
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 
      510060, China.
AD  - Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 
      Guangdong, 510060, China.
FAU - Lei, Yi-Yan
AU  - Lei YY
AD  - Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, Guangdong, 510080, China.
LA  - eng
PT  - Journal Article
DEP - 20231122
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10724660
OTO - NOTNLM
OT  - Hypothyroidism
OT  - Lung cancer
OT  - Mendelian randomization analysis
OT  - Oxidative stress
OT  - PI3K/Akt signaling
OT  - Transcriptome analysis
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/12/18 06:42
MHDA- 2023/12/18 06:43
PMCR- 2023/11/22
CRDT- 2023/12/18 04:55
PHST- 2023/06/30 00:00 [received]
PHST- 2023/11/14 00:00 [revised]
PHST- 2023/11/16 00:00 [accepted]
PHST- 2023/12/18 06:43 [medline]
PHST- 2023/12/18 06:42 [pubmed]
PHST- 2023/12/18 04:55 [entrez]
PHST- 2023/11/22 00:00 [pmc-release]
AID - S2405-8440(23)09869-9 [pii]
AID - e22661 [pii]
AID - 10.1016/j.heliyon.2023.e22661 [doi]
PST - epublish
SO  - Heliyon. 2023 Nov 22;9(12):e22661. doi: 10.1016/j.heliyon.2023.e22661. 
      eCollection 2023 Dec.