DNA Repair Patterns May Predict Risk of Pancreatic Cancer

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.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. The AACR’s most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.