Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 11;5(1):100254.
doi: 10.1016/j.xhgg.2023.100254. Epub 2023 Nov 3.

Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias

Tianzhong Yang  1 , Lauren J Mills  2 , Aubrey K Hubbard  3 , Rui Cao  4 , Andrew Raduski  2 , Mitchell J Machiela  3 , Logan G Spector  5
Affiliations

Genetic analyses identify evidence for a causal relationship between Ewing sarcoma and hernias

Tianzhong Yang et al. HGG Adv. .

Abstract

Knowledge of Ewing sarcoma (EWS) risk factors is exceedingly limited; however, multiple small, independent studies have suggested a possible connection between hernia and EWS. By leveraging hernia summary statistics from the UK Biobank and a recently published genome-wide association study of EWS (733 EWS cases and 1,346 controls), we conducted a genetic investigation of the relationship of 5 hernia types (diaphragmatic, inguinal, umbilical, femoral, and ventral) and EWS. We discovered a positive causal relationship between inguinal hernia and EWS (OR 1.27, 95% confidence interval [CI] 1.01-1.59, and p = 0.041) through Mendelian randomization analysis. Further analyses suggested shared pathways through three genes: HMGA2, LOX, and FBXW7. Diaphragmatic hernia showed a stronger causal relationship with EWS among all of the hernia types (OR 2.26, 95% CI 1.30-3.95, p = 0.004), but no statistically significant local correlation pattern was observed. No evidence of a causal or genetic relationship was observed between EWS and the other three hernia types, including umbilical hernia, despite a previous report indicating an OR as high as 3.3. The finding of our genetic analysis provided additional support to the hypothesis that EWS and hernias may share a common origin.

Keywords: Ewing sarcoma; GWAS; Mendelian randomization; diaphragmatic hernia; genome-wide association study; germline genetics; inguinal hernia.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1
Figure 1
Genetic correlation among five hernia types and EWS ∗∗ indicates statistical significance after Bonferroni correction; ∗ indicates marginal significance with p < 0.05.
Figure 2
Figure 2
MR plots for diaphragmatic hernia (A) Scatterplot for different MR methods, (B) Forest plot for relationship between diaphragmatic hernia and EWS for each single instrumental variable. Each black point and error bars in A/B represent point estimate of a single instrumental variable and standard error/95% confidence interval, respectively. Slope of lines in (A) corresponds to the estimated causal effect from different MR methods. Red points in (B) represents the combined causal estimate using all SNPs together using MR-Egger and IVW methods.
Figure 3
Figure 3
MR plots for inguinal hernia (A) Scatterplot for different MR methods, (B) Forest plot for relationship between diaphragmatic hernia and EWS for each single instrumental variable. Each black point and error bars in A/B represent point estimate of a single instrumental variable and standard error/95% confidence interval, respectively. Slope of lines in (A) corresponds to the estimated causal effect from different MR methods. Red points in (B) represents the combined causal estimate using all SNPs together using MR-Egger and IVW methods.
See this image and copyright information in PMC

References

    1. Valery P.C., Holly E.A., Sleigh A.C., Williams G., Kreiger N., Bain C. Hernias and Ewing’s sarcoma family of tumours: A pooled analysis and meta-analysis. Lancet Oncol. 2005;6:485–490. - PubMed
    1. Cope J.U., Tsokos M., Helman L.J., Gridley G., Tucker M.A. Inguinal hernia in patients with Ewing sarcoma: A clue to etiology. Med. Pediatr. Oncol. 2000;34:195–199. - PubMed
    1. He D., Hansen J., Federman N., Olsen J., Ritz B., Heck J.E. Abstract 5778: Hernia and Ewing sarcoma. Cancer Res. 2020;80 5778–5778.
    1. Winn D.M., Li F.P., Robison L.L., Mulvihill J.J., Daigle A.E., Fraumeni J.F. A Case-Control Study of the Etiology of Ewing’s Sarcoma. Cancer Epidemiol. Biomarkers Prev. 1992;1:525–532. - PubMed
    1. Valery P.C., McWhirter W., Sleigh A., Williams G., Bain C. A national case-control study of Ewing’s sarcoma family of tumours in Australia. Int. J. Cancer. 2003;105:825–830. - PubMed

MeSH terms