Defect in DNA repair system may be an advantage in colon cancer

Persons with colorectal cancer who have defects in their DNA mismatch repair (MMR) system have lower rates of tumor recurrence, longer remissions, fewer metastases, and better survival rates than patients who do not have this deficiency.

Approximately 15% of colorectal cancers develop due to defective function of the DNA MMR system, explained Frank A. Sinicrope, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues in the Journal of the National Cancer Institute. However, it was not known whether MMR status was linked to cancer recurrence rates.

To explore this issue, the group analyzed data from 2,141 patients from clinical trials who had undergone chemotherapy with the standard agent 5-fluorouracil (5-FU) after surgery for stage II or stage III colon cancer.

Deficient MMR (dMMR) was detected in 344 (16.1%) of the tumors. The deficiency was associated with a 5-year recurrence rate of 33%, compared with 22% for proficient MMR (pMMR) status. The dMMR group also had fewer distant recurrences than the pMMR patients (22% vs 12%) and a longer delay in time to recurrence.

The influence of MMR status on response to 5-FU has been in question; in this study, 5-FU therapy reduced recurrence rates in stage III disease, regardless of MMR status, but not in stage II patients.

“The results of this article by Sinicrope [and colleagues] provide valuable information about the prognostic and certainly the predictive role of dMMR,” wrote Sabine Tejpar, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium, and colleagues in an accompanying editorial (http://jnci.oxfordjournals.org/content/early/2011/05/19/jnci.djr170.full.pdf+html).

The editorial writers contend that these “hypothesis-generating” findings need to be validated in an independent dataset, adding, “It is important to consider whether these results are sufficient to validate MMR assessment as a prerequisite for selecting CRC patients for adjuvant therapy.”

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