Molecular characteristics and clinical outcomes of patients with gastroesophageal cancer diagnosed at ages younger than 50 years

Q: What was the study’s main objective regarding gastroesophageal cancer diagnosed before age 50?

To assess and compare clinicopathologic and molecular characteristics, and to identify factors associated with longer survival in patients diagnosed at ages younger than 50 versus those aged 50 and older.

Q: How were patients selected and what data source was used?

The analysis used Tempus’ clinicogenomic database and included patients who completed tumor molecular profiling between December 2017 and July 2024.

Q: What molecular differences were reported for patients diagnosed younger than 50 compared with those aged 50 and older?

The younger group showed lower rates of high tumor mutational burden and high microsatellite instability, and a higher incidence of somatic CDH1 mutations, with lower incidence of TP53, CDKN2A, and KRAS alterations.

Sep 22, 2026

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Incidence of gastroesophageal cancer diagnosed before age 50 is rising, yet clinicopathologic and molecular features in this subgroup remain insufficiently characterized. Using Tempus’ clinicogenomic database, the study compared patients diagnosed younger than 50 with those aged 50 and older who completed tumor molecular profiling from December 2017 to July 2024. Biomarker and alteration spectra were evaluated, and multivariate analysis assessed factors linked to longer survival. Results in 5,863 cases showed distinct molecular and survival associations in the younger group.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

JNCI Cancer Spectrum, 2026, 10(3), pkag034 [https://doi.org/10.1093/jncics/pkag034](https://doi.org/10.1093/jncics/pkag034) Advance Access Publication Date: April 6, 2026 Article Molecular characteristics and clinical outcomes of patients with gastroesophageal cancer diagnosed at ages younger than 50 years Michael H. Storandt , MD1, Emily A. Teslow , PhD2, Yingying Yu , MHS2, BinyamYilma , MPH2, Amit Mahipal , MD, MPH3, Zhaohui Jin , MD1, 􀀃 1Department of Oncology, Mayo Clinic, Rochester, MN, United States 2Tempus AI, Inc, Chicago, IL, United States 3Department of Medicine, Division of Hematology and Medical Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, United States 􀀃 Corresponding author: Zhaohui Jin, MD, Department of Medical Oncology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, United States ([jin.zhaohui@mayo.edu](jin.zhaohui@mayo.edu)) . Abstract Background: The incidence of gastroesophageal cancer diagnosed at ages younger than 50 years is increasing. Assessment of the clinicopathologic and molecular characteristics of these cancers is limited currently. Methods: This analysis used Tempus’ clinicogenomic database to compare patients diagnosed with gastroesophageal cancer at ages younger than 50 vs 50 years and older who completed tumor molecular profiling between December 2017 and July 2024. The spectrum of biomarkers, somatic alterations, and germline alterations were compared between those diagnosed with gastroesophageal cancer at ages younger than 50 years and those aged 50 years and older, and a multivariate analysis was conducted to identify factors associated with longer survival. Results: Among 5863 gastroesophageal cancer patients, 785 had gastroesophageal cancer diagnosed at ages younger than 50 years. There were more females (35% vs 25%, P < .001) and fewer White patients (69% vs 80%, P < .001) with gastroesophageal cancer at ages younger than 50 years. Fewer tumors of patients with gastroesophageal cancer at ages younger than 50 years had high tumor mutational burden (3.2% vs 10.2%, P < .001) or high microsatellite instability (1.7% vs 5.1%, P < .001), but there was no difference in PD-L1 positivity (49% vs 51%, P ¼ .3) . Higher incidence of somatic CDH1 mutations was seen in those with gastroesophageal cancer at ages younger than 50 years (16.1% vs 6.6%, q < 0.001) with lower incidence of TP53 (65.6% vs 74.1%), CDKN2A (12.5% vs 19.8%), and KRAS (11.7% vs 18.3%, P < .001 for all) alterations. The most statistically significant germline difference was higher incidence of CDH1 (2.2% vs 0.3%, q ¼ 0.001) and TP53 (0.6% vs 0%, q ¼ 0.039) alterations among those with gastroesophageal cancer at ages younger than 50 years. Median survival for patients with metastatic disease was longer for gastroesophageal cancer at ages younger than 50 years (11 vs 8.5 months, P ¼ .002), and gastroesophageal cancer at ages younger than 50 years, ERBB2 amplification, and high microsatellite instability were associated with superior survival. Conclusions: Unique molecular and germline profiles were seen in patients with gastroesophageal cancer at ages younger than 50 years, which may suggest differences in causal factors yet undiscovered. Introduction Gastroesophageal cancer constitutes a major global health problem. Globally, gastric and esophageal cancers are the 5th and 11th most commonly diagnosed cancers, and the 5th and 7th leading causes of cancer-related death, respectively.1-3 In the United States, gastric and esophageal cancers are less common and are the 16th and 20th most frequently diagnosed cancersand the 17th and 11th leading cause of cancer-related death, respectively.4 Despite lower incidence in the United States, it is still estimated that there will be 49 260 new gastroesophageal cancer cases, with 27 010 cancer-related deaths in the United States in 2024.5 In recent years, a concerning trend has been observed among newly

FAQs

What was the study’s main objective regarding gastroesophageal cancer diagnosed before age 50?

To assess and compare clinicopathologic and molecular characteristics, and to identify factors associated with longer survival in patients diagnosed at ages younger than 50 versus those aged 50 and older.

How were patients selected and what data source was used?

The analysis used Tempus’ clinicogenomic database and included patients who completed tumor molecular profiling between December 2017 and July 2024.

What molecular differences were reported for patients diagnosed younger than 50 compared with those aged 50 and older?

The younger group showed lower rates of high tumor mutational burden and high microsatellite instability, and a higher incidence of somatic CDH1 mutations, with lower incidence of TP53, CDKN2A, and KRAS alterations.

Sep 22, 2026

Upload by Chumphorn