Gene Studies Pinpoint Lung Cancer Mutation, Addiction Risk

By Anastacia Mott Austin

Scientists have long wondered why some heavy smokers get lung cancer while others do not. They have also tried to discover why some people who never smoked still develop the deadly disease.

This week, three studies have gotten them closer to the answers. Published in Nature and Nature Genetics, two of the studies have pinpointed mutations on gene number 15 (out of the 23 genes humans carry) which are associated both with a higher tendency to become addicted to smoking, as well as an increased risk, as high as 80%, of getting lung cancer. The teams used a method called genome-wide association, in which they scanned over 30,000 genetic markers and checked them for variations. While each small variation may not be significant, it is the combination of many different markers that makes for a predisposition for certain diseases.

Dr. Stephen J. Chanock, who represents the department of translational genomics and the National Cancer Institute, talked with reporters. "The effect of any one of these genetic markers is small, but we're looking at complex diseases where many genes have a role," said Dr. Chanock, who led one of the studies.

The third study also focuses on gene number 15 as an indicator of smoking addiction. The International Agency for Cancer Research conducted this study, and scientists were initially inclined to believe that the gene was associated with smoking addiction and increased risk of lung cancer because of the obvious connection with heavy smoking and lung cancer. But it appears that the predilection to become addicted to smoking is a separate phenomenon from the increased tendency to contract lung cancer. In other words, they are two separate findings.

Paul Brennan, leader of the IARC study, told reporters he thought the same thing at first. "The genes made you more likely to smoke, made you likely to smoke more, made you less likely to give up, and therefore more likely to develop lung cancer." But after completing the research, Brennan says he realized that they were two separate things. For example, though the gene might make someone more likely to become addicted to smoking, some with the gene do not take up smoking at all, yet are still at increased risk for lung cancer.

The researchers were careful to point out that none of their conclusions should give someone a false sense of security about lung cancer if the gene mutation is not present. Smoking is still the number one risk factor for contracting lung cancer, with or without the gene. The risk among the general population of smokers for later having lung cancer is about 14%, and in smokers with the gene mutation it’s 23%.

The recent studies echo many others which have ventured into gene-mapping territory. Experts in the field are hoping to eventually be able to give the general consumer a basic gene map of his or her own genetic makeup, predicting which diseases (or perhaps at some point, personality traits or quirks) could be inherited.

In fact, one of the research teams involved in the studies, deCODE Genetics from Iceland, has created a consumer package that they are ready to market to the public, in which genetic testing can be done for an individual’s risk for more than 26 different diseases, including cancer, diabetes, and even baldness.

Kari Steffanson, who co-wrote the report for deCODE, says he is concerned that people will see the test as an excuse to smoke if they don’t have the gene mutation for either addiction or lung cancer, something he sees as a mistake. "As a diagnostic test, I think, it is of no value," said Stefansson. "I am actually even a little bit afraid that some may look at it as a green light to smoke, and that's something I would not want to contribute to."