Mutation Patterns of DNA Repair Enzymes May Foretell Pancreatic Cancer Risk

Cancer researchers have found that the pattern of mutations in genes that produce DNA repair enzymes may be used to foretell increased or decreased risk of developing pancreatic cancer, depending on the genes involved.

As pancreatic cancer is often identified in late stages when it is resistant to most available therapies, there is considerable interest in characterizing genetic profiles that could be used to identify high-risk individuals for the purpose of prevention and early detection of this disease.

Toward this end, investigators at the University of Texas M. D. Anderson Cancer Center (Houston, USA) analyzed nine single nucleotide polymorphisms of seven DNA repair genes (LIG3, LIG4, OGG1, ATM, POLB, RAD54L, and RECQL) in 734 patients with pancreatic cancer and 780 healthy controls using the Taqman PCR (polymerase chain reaction) method for amplifying DNA expression. Information on cigarette smoking, alcohol consumption, medical history, and other risk factors was collected by personal interview. They reported in the January 15, 2009, issue of the journal Clinical Cancer Research that the presence of a homozygous mutant genotype of LIG3 G-39A was associated with a 77% reduction in the risk of pancreatic cancer. By contrast, the presence of the gene ATM D1853N was associated with a nearly threefold (255%) increased risk of pancreatic cancer.

"Currently, there is no approved genetic screening tool for pancreatic cancer," said first author Dr. Donghui Li, associate professor of gastrointestinal medical oncology at the M. D. Anderson Cancer Center. "Our study provides some preliminary data on one pattern of genetic variations that may be useful in determining risk. However, we still need to be cautious. As with any science, the key is replication, and the results of this study need to be confirmed by others."

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University of Texas M. D. Anderson Cancer Center