Variations in mismatch repair genes can help predict treatment response and prognosis in patients with pancreatic cancer, according to research from The University of Texas M. D. Anderson Cancer Center presented today in advance of the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
In the study, single nucleotide polymorphisms (SNPs) in genes involved in DNA mismatch repair were associated with response to gemcitabine (Gemzar)-based preoperative chemoradiation, tumor resectability (the likelihood of removing the entire tumor), and overall survival.
"Gemcitabine is a major chemotherapeutic agent used to treat pancreatic cancer, but we don't understand why some patients respond and most patients do not," said Donghui Li, Ph.D., the study's lead author and professor in M. D. Anderson's Department of Gastrointestinal Medical Oncology. "There has been no biomarker for pancreatic cancer used in the clinic to predict response. Our research interest has been to determine whether genetic variation in DNA repair can be a predictor of treatment response or a prognosis factor for patient survival."
DNA repair is a complicated process, Li noted, with various mechanisms responsible for identifying and correcting different types of DNA damage. Mismatch repair genes correct mistakes in DNA replication or trigger cell death (apoptosis) if repair is not possible. Ensuring cell death is critical to preventing the runaway cell division that occurs in malignant tumors.
In the study, Li's group obtained DNA samples from 154 patients with potentially resectable pancreatic adenocarcinomas who were participating in phase II clinical trials of preoperative gemcitabine-based chemoradiation. The researchers evaluated 15 SNPs (also called genotypes) among eight mismatch repair genes (EXO1, MLH1, MSH2, MSH3, MSH6, PMS1, TREX1, and TP73) and correlated them with tumor response to gemcitabine, the likelihood of achieving complete tumor resection, and overall survival.