Genetic variations in DNA repair patterns may increase risk of pancreatic cancer

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Genetic variations in DNA repair patterns may increase risk of pancreatic cancer by as much as threefold or decrease it by as much as 77 percent, depending on the genes involved, according to a report published in the January 15, 2009, issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.

Pancreatic cancer is often identified in late stages, and thus is resistant to most available therapies. Scientists like Donghui Li, Ph.D., a professor in the Department of Gastrointestinal Medical Oncology at The University of Texas M. D. Anderson Cancer Center, are working to determine genetic profiles that can be used in identifying high-risk individuals for the purpose of prevention and early detection of this disease.

"Our study provides some preliminary data on one pattern of genetic variations that may be useful in determining risk," said Li, who is the lead author on the Clinical Cancer Research paper. "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."

Li and colleagues analyzed nine single nucleotide polymorphisms of seven DNA repair genes among 734 patients with pancreatic cancer and 780 people without cancer. DNA repair is the guardian of the genome. When DNA repair failed to fix the DNA damages caused by exogenous agents such as tobacco carcinogens or endogenous agents such as reactive oxygen species, there is an increased chance of getting cancer.

Researchers found that the presence of a homozygous mutant genotype of LIG3 G-39A was associated with a 77 percent reduction in the risk of pancreatic cancer. By contrast, the presence of the gene ATM D1853N was associated with a nearly threefold (255 percent) increased risk of pancreatic cancer.

Currently, there is no approved genetic screening tool for pancreatic cancer, Li said.

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