Genetically predicted high circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 increase the risks of soft tissue sarcoma.
IGF-1
IGFBP-3
SNP
Soft tissue sarcoma
genetic risk score
Journal
American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
02
2021
accepted:
13
04
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
16
9
2021
Statut:
epublish
Résumé
Insulin growth factor-1 (IGF-1) plays important roles in carcinogenesis. Previous studies have linked circulating IGF-1 and its main binding protein, insulin-like growth factor-binding protein-3 (IGFBP-3), to cancer risks. However, no study has been conducted in soft tissue sarcoma (STS). In this study, we investigated the relationship of genetically predicted circulating IGF-1 and IGFBP-3 with STS risks. Recent large genome-wide association studies (GWAS) have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. We genotyped these SNPs in 821 patients and 851 healthy controls. We constructed weighted genetic risk scores (GRS) to predict circulating IGF-1 and IGFBP-3. We determined the associations of individual SNPs and GRS with the risks of STS using multivariate logistic regression analysis. We found high genetically predicted circulating IGF-1 and IGFBP-3 were both associated with increased STS risks. Dichotomized at the median values of IGF-1 and IGFBP-3 in controls, individuals with high level of IGF-1 exhibited a 27% increased risk of STS (odds ratio [OR]=1.27, 95% confidence interval [CI]=1.04-1.54, P=0.017), whereas the OR for high IGFBP-3 was 1.45 (95% CI=1.20-1.77, P<0.001). Interestingly, the significant association between IGFBP-3 and STS risk was only evident in women (OR=1.88, 95% CI=1.42-2.49, P<0.001), but not in men (OR=1.00, 95% CI=0.75-1.33, P=0.992). In stratified analyses by major STS subtypes, the strongest associations were observed in angiosarcoma for IGF-1, leiomyosarcoma for IGFBP-3, and gastrointestinal stromal tumors for IGFBP-3 in women. In conclusion, high circulating IGF-1 and IGFBP-3 levels were both associated with increased STS risks.
Types de publication
Journal Article
Langues
eng
Pagination
3980-3989Informations de copyright
AJCR Copyright © 2021.
Déclaration de conflit d'intérêts
None.
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