Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes

TL;DR

This paper explores how inherited bone marrow failure syndromes increase the risk of colorectal cancer, suggesting the need for early and tailored screening in affected patients.

Contribution

The paper highlights the link between specific bone marrow failure syndromes and colorectal cancer, emphasizing the need for targeted surveillance strategies.

Findings

IBMFS patients, especially those with DBAS and FA, show an increased risk of developing colorectal cancer at younger ages.

Genomic instability due to DNA repair defects and telomere dysfunction contributes to CRC in IBMFS patients.

The findings suggest a need for earlier and more intensive CRC screening protocols for IBMFS individuals.

Abstract

Inherited Bone Marrow Failure Syndromes (IBMFS) encompass a group of rare genetic disorders characterized by intrinsic hematopoietic stem cell defects, leading to impaired hematopoiesis and increased predisposition to malignancies, particularly hematologic cancers. As advances in supportive care and hematopoietic stem cell transplantation have extended patient survival, there is growing recognition of an elevated risk of solid tumors, including colorectal cancer (CRC), within this population. Epidemiologic data, although limited by small cohort sizes, suggest the need for earlier and more intensive CRC surveillance protocols tailored to IBMFS patients, who tend to develop CRC at younger ages compared to the general population. Among IBMFS, the most robust association with CRC has been reported in Diamond–Blackfan anemia syndrome (DBAS) and Fanconi anemia (FA), while emerging evidence suggests a potential link in dyskeratosis congenita (DC) and Shwachman–Diamond syndrome (SDS). The pathophysiological basis involves defective DNA repair mechanisms, telomere dysfunction, ribosomal protein abnormalities, and impaired cellular stress responses, each contributing to genomic instability and malignant transformation. The understanding of the molecular mechanisms underpinning the association between IBMFS and CRC may provide a foundation for future targeted prevention and surveillance strategies and offer broader insights into colorectal carcinogenesis.

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