Johns Hopkins Magazine - June 1995 Issue

Molecular Evidence Ties Smoking to Cancer

By Melissa Hendricks

A Hopkins research team reports the strongest cause-and-effect relationship between cigarette smoking and cancer "that really nails it at the molecular level," says principal investigator David Sidransky, associate professor of otolaryngology and oncology. "This is no longer just an association."

Though many epidemiological studies have implicated cigarette smoking as a cause of cancer, critics of those studies point out that the evidence is circumstantial. In other words, studies that find high rates of cancer among people who smoke do not prove that smoking causes cancer. Though it may seem unlikely, the real carcinogenic culprit could be something else. But molecular evidence does not have that limitation.

Sidransky's finding reveals that smoking dramatically increases mutations in a gene called p53 that normally suppresses the growth of cancer. Mutations in p53, the most common genetic mutation in cancer, are believed to contribute to cancer's inception and growth. Carcinogens in cigarette smoke appear to "knock out" the healthy p53 gene, says Sidransky. Furthermore, his study also indicates that alcohol abets the process, perhaps by destroying the mucosa to clear a passage for the absorption of carcinogens.

Sidransky and his colleagues examined tumor samples from 129 head and neck cancer patients. Patients who smoked at least a pack a day for at least 20 years were twice as likely as non-smokers to have mutations in p53, the researchers found. Patients who smoked and drank more than an ounce of hard alcohol daily were 3.5 times as likely as those who neither smoked nor drank to have mutations in p53.

While 33 percent of the patients who smoked and 58 percent of the patients who smoked and used alcohol had mutations in the p53 gene, only 17 percent of the patients who neither smoked nor drank had p53 mutations. Among this subset of non-smokers, all of the mutations occurred in "hotspots," areas that are prone to randomly occurring mutations. Among smokers, only 23 percent of the p53 mutations occurred in these regions. The rest appeared in areas that don't typically mutate by chance - - only as the result of an environmental trigger like carcinogens from cigarette smoke.

While smoking has been most widely publicized as a cause of lung cancer, it's also been implicated in a slew of diseases, including bladder and head and neck cancers. According to the American Cancer Society, each year in the United States, 50,000 people die from head and neck cancers, which include cancers of the lip, mouth, throat, and voice box.

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