Genetic cause of 15% of all colorectal cancer diagnoses identified.
Colorectal cancer is the development of cancer from the colon or rectum, due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time. Up to 15% of colorectal cancers show a genetic mutation known as DNA mismatch repair deficiency, or dMMR. However, little is known about how the mutation behaves in rectal cancer patients, what causes dMMR, or which treatments may be most effective. Now, a study from researchers at the MD Anderson Cancer Center uncovers new data about dMMR’s hereditary basis in rectal cancer. The team state that their findings may guide physicians in diagnoses, preventive measures, and in exploring of potential new therapy options.
Previous studies show that DNA mismatch repair is the body’s method for repairing mutations or gene defects that occur during cell division. Sometimes things go awry with this vital tool, resulting in increased mutations and cancer. Four genes, MLH1, MSH2, MSH6 and PMS2, previously have been associated with DNA mismatch repair. Until now, researchers believed MLH1 and MSH2 were the main culprits causing the DNA repair machinery to break down. The current study shows, in fact, it is MSH2 and MSH6 that are most commonly found among dMMR rectal cancer patients.
The current study examines 62 patient records from 1992 to 2012 to identify MSH2 and MSH6 as genes with mutations that patients can potentially pass on to family members is key to offering improved identification and surveillance for patients and family members at risk for dMMR. Results show that the median age at diagnosis was 41 years and dMMR deficiency was most commonly due to alterations in MSH2 or MSH6. Data findings show that after a median follow-up of 6.8 years, the 5-year rectal cancer–specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease.
The lab state that between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. They go on to add that oncologic treatment and outcomes as well as clinical genetics work-up were examined, with overall and rectal cancer–specific survival calculated by the Kaplan-Meier method.
The team surmise that their findings provide a benchmark for current treatment approaches including chemotherapy and surgery and confirmed dMMR patients likely are to have a good prognosis. They go on to add that their study also highlights the need to pay attention to long-term care after surviving rectal cancer. For the future, the researchers state that their results provide a perfect illustration of how the power of precision medicine can be realized. They conclude that this new genetic understanding of dMMR provides implications for telling patients how well they will do long-term and for choosing the best surgical and chemotherapy options.