Alcohol Impairs Tumor-Suppressing Gene in Smokers

Drinking alcohol dramatically boosts the risk of a common gene mutation in smokers developing lung cancer, according to researchers at the Medical College of Wisconsin and The Johns Hopkins School of Medicine. Steven A. Ahrendt, MD, formerly an Assistant Professor of Hepatobiliary/Endocrine Surgery at the Medical College; David Sidransky, MD, from The Johns Hopkins School of Medicine, and their colleagues reported their findings in the journal Cancer Research.

They found that mutations in the gene known as p53 in the cancer cells of patients with the most common type of lung cancer were strongly associated with both cigarette smoking and alcohol use. Furthermore, patients developing lung cancer who regularly drank alcohol were nearly twice as likely to have mutations in the p53 gene than were non-drinkers who smoked and more than five times more likely to have these mutations than non-drinkers who didn't smoke.

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, and plays a significant role in the early events leading to the development of lung cancer, says Dr. Ahrendt.

"While our study did not demonstrate that drinking alcoholic beverages increases the risk of developing lung cancer, we did show that alcohol clearly increases the genetic damage caused by long-standing exposure to cigarette smoke," Dr. Ahrendt said.

The researchers found that 76% of patients who underwent surgery for non-small cell lung cancer and both smoked and drank had mutations in the p53 gene compared with 42% of patients who smoked but abstained from alcohol. Non-small cell lung cancer makes up approximately 80% of cases of lung cancer in the United States.

Seven percent of the surgical patients neither smoked nor drank, and only 14% of these patients had a mutation in the p53 gene. These patients had a form of lung cancer called adenocarcinoma, which is the most common type of lung cancer found in non-smokers.

While several studies have shown that heavy alcohol drinking does boost the lung cancer risk of smokers, this study is the first to show that alcohol, even though it does not cause mutations itself, does increase the mutation rate in the p53 gene caused by tobacco. The p53 gene normally suppresses cell growth, permitting repair of damaged DNA prior to cell division. Mutations in the gene impair that ability.

The researchers reported on the drinking and smoking habits of 105 patients who underwent surgery for lung cancer at The Johns Hopkins Medical Institutions. Ninety-five patients were smokers; 10 had never smoked. Patients were classified as alcohol drinkers if they consumed one or more glasses of beer, hard liquor or wine daily during the 20 years prior to the diagnosis of lung cancer. Each of the 95 smokers had smoked one pack of cigarettes per day for at least ten years. Fifty-six of the patients were men (two were non-smokers and non-drinkers); 49 were women (eight were non-smokers and non-drinkers).

The researchers say there are a number of possible mechanisms responsible for alcohol's ability to increase the risk of p53 mutations in smokers developing lung cancer.

They believe that alcohol and its breakdown products impair the function of enzymes involved in DNA repair. In addition, alcohol also affects the activity of several enzymes involved in detoxifying carcinogens found in tobacco smoke. The presence of alcohol may lead to an increase in the exposure of the lung to tobacco carcinogens.

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