Expert Reviewed By: Dr. Brandon Colby MD
Understanding APC-Mutation Negative Familial Colorectal Cancer
Colorectal cancer is a major global health concern, and in some cases, it runs in families. Familial colorectal cancer can be attributed to mutations in the adenomatous polyposis coli (APC) gene. However, some patients with a family history of colorectal cancer do not have identifiable APC gene mutations, leading to the classification of a subset of cases as APC-mutation negative familial colorectal cancer (APCmut- CRC).
Recent research has shed light on novel genetic and epigenetic mechanisms that contribute to the development of APCmut- CRC. For instance, a study identified a copy number variable region at 3q26 that regulates the expression of the tumor suppressor gene PPM1L. Another study found that a disruption in chromosome 19q13 alters the expression of several genes and long non-coding RNA (lncRNA), which could contribute to colorectal cancer development. Furthermore, a comprehensive review explored genotype-phenotype correlations in autosomal dominant and recessive APC mutation-negative colorectal adenomatous polyposis, concluding that multiple genes with different phenotypes interact in the pathogenesis of the disease.
Diagnosing APC-Mutation Negative Familial Colorectal Cancer
Diagnosing APCmut- CRC involves a combination of clinical evaluation, family history assessment, and genetic testing. In the absence of APC gene mutations, identifying the underlying genetic causes can be challenging. However, recent advances in genomic technologies have enabled the identification of novel genetic alterations associated with APCmut- CRC, such as the copy number variable region at 3q26 and the chromosome 19q13 disruption.
Uses of Genetic Testing for APC-Mutation Negative Familial Colorectal Cancer
Genetic testing plays a crucial role in the diagnosis and management of APCmut- CRC. Some of the key uses of genetic testing for this disorder include:
- Identification of at-risk family members: Genetic testing can help identify family members who carry the genetic alterations associated with APCmut- CRC, allowing for early detection and intervention.
- Guiding treatment decisions: Understanding the specific genetic alterations in a patient's cancer can help healthcare providers tailor treatment strategies to target the underlying molecular drivers of the disease. For example, a study identified two groups of APCmut- CRCs characterized by enhanced mitochondrial activation or increased sensitivity to extracellular WNT, suggesting potential susceptibility to inhibition of these pathways.
- Monitoring disease progression: Genetic testing can be used to track the evolution of a patient's cancer over time, providing valuable information for disease management and treatment planning.
- Informing reproductive decisions: For individuals with a family history of APCmut- CRC, genetic testing can provide information on the risk of passing the genetic alterations to their children, aiding in informed family planning.
Conclusion
APC-mutation negative familial colorectal cancer is a complex and heterogeneous disease with diverse genetic and epigenetic mechanisms at play. Advances in genomic technologies have enabled the identification of novel genetic alterations associated with this disorder, paving the way for improved diagnosis, risk assessment, and targeted treatment strategies. Genetic testing is an invaluable tool in the management of APCmut- CRC, with applications ranging from identifying at-risk family members to guiding treatment decisions and monitoring disease progression.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)