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Publications

Journal Article Epublish

PubMed: 42147237 DOI: 10.3389/fonc.2026.1792016

Comparative molecular analysis of colorectal cancer in Saudi Arabia: distinct genetic alterations and clinical features.

Front Oncol 16:1792016

Authors: Maha-Hamadien Abdulla, Jumanah Yousef Alshenaifi, Mansoor-Ali Vaali-Mohammed, Ahmad Zubaidi, Khayal Al Khayal, Noura S Alhassan, Khalid Abdulrahman Al-Saleh, Omar Al Obeed, Scott Kopetz

Affiliations

  • Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • Department of Pathology, College of medicine, King Saud University, Riyadh, Saudi Arabia.
  • Department of Medicine, Oncology Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Abstract

PURPOSE

Globally, colorectal cancer (CRC) stands as the third most common type of cancer, a ranking that has remained consistent over recent years. However, the scenario diverges in Saudi Arabia, where CRC ascends to the forefront as the most common cancer among males and the second most prevalent among females. This discrepancy is primarily driven by male demographics, with a staggering 73% of cases diagnosed at a late stage, underscoring a critical public health concern. Delving into the molecular and phenotypic profiles of CRC within the Saudi populace emerges as a crucial stride towards addressing the escalating disease burden afflicting the country.

METHODS

To unravel the CRC driver molecular landscapes among the Saudi population, we performed Whole Exome Sequencing (WES) of 50 Saudi CRC patients collected by the Colorectal Cancer Research Center at King Saud University Medical Center (KSUMC) with MSS adenocarcinoma tumors. These patients were compared with comparable tumor cohorts from MD Anderson Cancer Center (MDACC) and The Cancer Genome Atlas (TCGA).

RESULTS

Tumors from Saudi patients have a significantly lower frequency of KRAS mutations (6.5% vs. 45.0% MDACC and 41.1% TCGA, with a p-value < 0.001), APC mutations (47.8% vs. 77.9% MDACC and 79% TCGA, with a p-value of less than 0.001) and CTNNB1 mutations (0% vs. 2.3% MDACC and 10% TCGA, with a p-value < 0.001). However, TP53 mutations were more common (50.0% vs. 35.9% MDACC and 43.0% TCGA, p-value < 0.05). The proportion of Saudi CRC patients who have sigmoid disease is higher (41.7% vs. 24.4% at MDACC) and they tend to be significantly younger (58 vs. 62 MDACC and 68 TCGA).

CONCLUSION

The results indicate a distinct mutational landscape of CRC in Saudi Arabia, highlighting the importance of gathering population-specific data in order to inform diagnostic of molecular cancer screening and treatment strategies for patients in Saudi Arabia.

MeSH

Neoplasms, Colorectal Neoplasms, Mutation