PMID- 35530326
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Fasting Insulin and Risk of Overall and 14 Site-Specific Cancers: Evidence From 
      Genetic Data.
PG  - 863340
LID - 10.3389/fonc.2022.863340 [doi]
LID - 863340
AB  - OBJECTIVE: Whether fasting insulin (FI) plays a role in cancer risk remains 
      unclear. This study aimed to investigate the association between FI and cancer 
      risk and to explore its potential mediator role in the association between type 2 
      diabetes mellitus (T2DM) and cancer. METHODS: Two-sample Mendelian randomization 
      (TSMR) analysis was performed to evaluate the effect of FI on overall and 14 
      site-specific cancers using genome-wide association study (GWAS) summary-level 
      data from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) 
      and consortia of 14 site-specific cancers. The primary MR approach was conducted 
      by using the random-effect inverse-variance weighted (IVW) method, and 
      sensitivity analyses were implemented by adopting weighted-median, weighted-mode, 
      MR-Egger, and MR-PRESSO tests. Polygenic risk score analysis was executed by 
      using individual-level data from UK Biobank to validate the findings from TSMR 
      analyses. Multivariable Mendelian randomization (MVMR) was carried out to 
      estimate the mediation effect of FI on the association between T2DM and cancer. 
      RESULTS: TSMR study suggested that genetically determined high FI levels were 
      associated with increased risk of colorectal cancer (odds ratio (OR) = 1.87, 95% 
      CI: 1.23-2.84, p = 0.003) and endometrial cancer (OR = 1.89, 95% CI: 1.08-3.01, p 
      = 0.008), but not associated with overall cancer risk or the other 12 studied 
      cancer sites. Polygenic risk score analysis successfully replicated the 
      association between genetic liability to high FI levels and the increased risk of 
      colorectal and endometrial cancers. MVMR and MR mediation analyses detected an 
      intermediary effect of FI and quantified that FI mediated 21.3% of the 
      association between T2DM and endometrial cancer. CONCLUSIONS: This study 
      demonstrated that FI levels are associated with the risk of colorectal and 
      endometrial cancers, and FI was found to play an intermediary role in the 
      association between T2DM and endometrial cancer. The associations between FI and 
      other cancers need to be further studied.
CI  - Copyright (c) 2022 Zhang, Li, Liu, Wan, Yu, Wang and Li.
FAU - Zhang, Han
AU  - Zhang H
AD  - Henan Provincial People's Hospital, Zhengzhou University, Henan, China.
AD  - College of Public Health, Zhengzhou University, Henan, China.
FAU - Li, Doudou
AU  - Li D
AD  - Henan Provincial People's Hospital, Zhengzhou University, Henan, China.
AD  - College of Public Health, Zhengzhou University, Henan, China.
FAU - Liu, Xiaozhuan
AU  - Liu X
AD  - Henan Provincial People's Hospital, Zhengzhou University, Henan, China.
FAU - Wan, Zhongxiao
AU  - Wan Z
AD  - College of Public Health, Zhengzhou University, Henan, China.
FAU - Yu, Zengli
AU  - Yu Z
AD  - College of Public Health, Zhengzhou University, Henan, China.
FAU - Wang, Yuming
AU  - Wang Y
AD  - Henan Provincial People's Hospital, Zhengzhou University, Henan, China.
FAU - Li, Xue
AU  - Li X
AD  - Henan Provincial People's Hospital, Zhengzhou University, Henan, China.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20220421
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9069016
OTO - NOTNLM
OT  - Mendelian randomization study
OT  - cancer
OT  - fasting insulin
OT  - polygenic risk score analysis
OT  - type 2 diabetes
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/10 06:00
MHDA- 2022/05/10 06:01
PMCR- 2022/01/01
CRDT- 2022/05/09 04:21
PHST- 2022/01/27 00:00 [received]
PHST- 2022/03/22 00:00 [accepted]
PHST- 2022/05/09 04:21 [entrez]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/05/10 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.863340 [doi]
PST - epublish
SO  - Front Oncol. 2022 Apr 21;12:863340. doi: 10.3389/fonc.2022.863340. eCollection 
      2022.