Systematic Review and Meta-analysis of the Most Common Genetic Mutations in Esophageal Squamous Cell Carcinoma

Purpose Esophageal cancer is the second most common cancer among men and women. There is a need to systematically assess the current evidence to map out the contribution of genetic factors in the development of esophageal squamous cell carcinoma (ESCC). Methods A literature search was carried out on published and unpublished studies up to August 2021 in Medline (PubMed), Embase (Ovid), Scopus, Proquest, Web of Science, and Google scholar. Studies that have reported the frequency of genetic mutations in ESCC were included in this study. Results A total of 1238 titles were retrieved through searches, and finally, 56 articles, including 8114 samples, met our predefined inclusion criteria. Of the included studies, 31 were conducted in China, 12 in Japan, and the remaining were conducted in various nations, including Brazil, Korea, and Iran. Most of our included studies evaluated the TP53 (n = 37 studies) and PIK3CA (n = 30 studies) gene mutations. TP53 (68.6%; 95% CI: 61.6-74.9), CCND1 (39.3%; 95% CI: 26.2-54.1), MDM2 (24.9%; 95% CI: 9.5-51.0), NOTCH1/2/3 (17.9%; 95% CI: 15.0-21.2), KMT2D (17.4%; 95% CI: 12.4-23.8), CDKN2A (15.0%; 95% CI: 8.1-26.1), PIK3CA (13.8%; 95% CI: 10.3-18.1), FAT1 (13.3%; 95% CI: 11.7-15.0), and EGFR (9.9%; 95% CI: 5.6-17.0) were the most common involved genetic factors in developing ESCC. Conclusion This systematic review and meta-analysis revealed that more than 10% of ESCC patients had changes in TP53, CCND1, MDM2, NOTCH1/2/3, KMT2D, CDKN2A, PIK3CA, and FAT1 genes, which can highlight their role in developing ESCC. TP53, CCND1, and MDM2 are the most prevalent, demonstrating 68.6%, 39.3%, and 24.9% of the mutations in ESCC patients.

Automated summary

Esophageal cancer is the second most common cancer, and this study aimed to assess the contribution of genetic factors in the development of esophageal squamous cell carcinoma (ESCC). The systematic review identified TP53, CCND1, and MDM2 as the most prevalent genetic mutations in ESCC patients, highlighting their role in the disease.