Researchers at the The University of Texas MD Anderson Cancer Center found a set of genes, previously assumed to play a negligible role, to be responsible for a machinery allowing the formation of mutations in genes linked to rectal cancer — the DNA mismatch repair system.
The findings, presented in the report “DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics,” published in the Journal of Clinical Oncology, can help physicians in setting diagnoses, as well as choosing treatments for their rectal cancer patients.
Scientists have known that in about 15 percent of colorectal cancer patients, mutations leading to a condition called DNA mismatch repair deficiency can be linked to the cancer.
When cells divide and chromosomes are copied and duplicated, occasional errors during the copy process lead to mutations in the new chromosomes. The body, however, has a quality control system, the DNA mismatch repair, making sure such errors are corralled. When the tool itself becomes dysfunctional, the risk of developing cancer quickly escalates.
While four genes are known to control the system, earlier research suggested that two of them — MLH1 and MSH2 — were involved in the breakdown of the system.
Studying medical records of 62 patients with colorectal cancer, the research team, led by Dr. Nancy You, discovered that it was another set of genes that was involved in this group of patients: MSH2 and MSH6.
The team also noted that patients with a mismatch repair deficiency, despite the increased risk for cancer, had a better prognosis. You believes the findings will allow physicians to better tailor treatment to individual patients based on the genetic profile of the tumor. This aligns with President Obama’s Precision Medicine Initiative, launched in 2015.
“Our paper provides a perfect illustration of how the power of precision medicine can be realized,” You, an associate professor of surgical oncology, said in an MD Anderson news release. “This new genetic understanding of DNA mismatch repair deficiency provides immediate implications for telling patients how well they will do long-term and for choosing the best surgical and chemotherapy options.”
“If we know a patient carries this mutation, then we can enroll them in our Familial High-Risk GI [Gastrointestinal] Cancer Clinic, where we follow them and their at-risk family members and conduct cancer surveillance tests to detect pre-cancerous lesions and remove them as early as we can,” You said, adding that “there is some evidence that lifestyle choices still matter even in this genetic disease.”