Two genes may interact to increase risk of lung cancer in smokers

WASHINGTON, July 13 Researchers have long sought to explain why some smokers get lung cancer and others do not. In one of the first studies to suggest that the interaction of two genes may play a role, researchers at the University of Pittsburgh Cancer Institute (UPCI) have found that inheriting alterations in both a DNA repair gene and a cyclin D1 gene may increase the risk of lung cancer in those exposed to tobacco carcinogens. The preliminary findings are being presented at a poster session at the rescheduled annual meeting of the American Association for Cancer Research (AACR) on Sunday, July 13, in Washington, D.C.

"In our study, we found a strong correlation between genetic polymorphisms in two genes and lung cancer risk," said Marjorie Romkes, Ph.D., study co-investigator and associate professor, Center for Clinical Pharmacology, department of medicine and director, General Clinical Research Center Pharmacogenetics Care Laboratory, University of Pittsburgh. "Our findings, while preliminary, suggest that the co-inheritance of mutations in a DNA repair gene called XPD and the cyclin D1 gene may be linked to increased risk of lung cancer in those exposed to tobacco smoke. While we have known that these genes are linked to lung cancer on their own, this is the first time we have observed that they may interact to increase lung cancer risk."

The study compared 173 patients with lung cancer to a control group of 184 healthy individuals and found that mutations in both XPD and cyclin D1 (CCND1) occurred more often in the lung cancer patients. In addition, a strong increase in lung cancer risk was observed among individuals with a smoking history and a combination of mutations in both the XPD and CCND1 genes. Those with a smoking history had an odds ratio of 17.0 compared to non-smokers who had an odds ratio of 6.3.

"These findings are important because they have the potential to help us identify those smokers who have a greater likelihood

Contact: Clare Collins or Jocelyn Uhl
University of Pittsburgh Medical Center

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