Expert Reviewed By: Dr. Brandon Colby MD
Hereditary nonpolyposis colorectal neoplasms (HNPCC) are a group of inherited conditions that increase the risk of developing colorectal cancer. Also known as Lynch syndrome, HNPCC is the most common form of hereditary colorectal cancer, accounting for about 2-4% of all cases. This article aims to provide a comprehensive understanding of HNPCC, its diagnosis, and the role of genetic testing in managing this condition.
What is Hereditary Nonpolyposis Colorectal Neoplasms (HNPCC)?
HNPCC is a genetic disorder that increases the risk of developing colorectal cancer, as well as other types of cancer, such as endometrial, ovarian, gastric, and urinary tract cancers. It is caused by mutations in specific genes responsible for repairing errors in DNA replication. These mutations lead to an accumulation of DNA errors, which can cause cells to grow and divide uncontrollably, forming tumors.
Diagnosing HNPCC
Diagnosing HNPCC can be challenging, as there are no specific symptoms that distinguish it from sporadic colorectal cancer. However, certain factors may raise suspicion of HNPCC, such as:
- A family history of colorectal cancer, particularly at a young age
- Multiple family members with colorectal cancer or other HNPCC-related cancers
- A personal history of colorectal cancer or HNPCC-related cancers at a young age
If HNPCC is suspected, further evaluation may include a detailed family history, medical records review, and genetic testing.
Genetic Testing for HNPCC
Genetic testing plays a crucial role in diagnosing HNPCC and managing the condition. There are several uses of genetic testing in the context of HNPCC, which are discussed below.
Confirming a Diagnosis
Genetic testing can confirm a diagnosis of HNPCC by identifying mutations in the genes associated with the condition. The most common genes involved in HNPCC are MLH1, MSH2, MSH6, and PMS2. Identifying a mutation in one of these genes can confirm the diagnosis and help guide treatment and management decisions.
Identifying At-Risk Family Members
Once a mutation has been identified in an individual with HNPCC, genetic testing can be offered to at-risk family members. This can help identify those who have inherited the mutation and are at an increased risk of developing colorectal cancer. Early identification of at-risk individuals allows for appropriate surveillance and preventive measures to be implemented, reducing the risk of cancer development.
Guiding Treatment Decisions
Genetic testing can also help guide treatment decisions for individuals with HNPCC-related cancers. For example, some studies have suggested that individuals with HNPCC may respond differently to certain chemotherapeutic agents, such as 5-fluorouracil. Identifying the specific gene mutation involved in HNPCC can help tailor treatment plans to the individual's unique genetic profile.
Surveillance and Prevention
For individuals with HNPCC, regular surveillance is essential for early detection and prevention of colorectal cancer. Genetic testing can help determine the appropriate surveillance schedule based on the specific gene mutation involved. In general, individuals with HNPCC should undergo colonoscopy every 1-2 years, starting at age 20-25 or 10 years earlier than the youngest age of colorectal cancer diagnosis in the family. Additional screening for other HNPCC-related cancers may also be recommended.
Reproductive Decision-Making
Genetic testing can also inform reproductive decision-making for couples who both carry an HNPCC gene mutation. Prenatal testing or preimplantation genetic diagnosis (PGD) can be used to determine if an embryo has inherited the HNPCC mutation, allowing couples to make informed decisions about their family planning.
In conclusion, understanding and diagnosing hereditary nonpolyposis colorectal neoplasms is crucial for effective management of the condition. Genetic testing plays a vital role in confirming the diagnosis, identifying at-risk family members, guiding treatment decisions, and informing surveillance and prevention strategies. By leveraging genetic testing, individuals with HNPCC can take proactive steps to reduce their risk of developing colorectal cancer and improve their overall quality of life.
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)