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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Genetics, Family History, and Lung Cancer
Sun, 06/17/2007 - 21:25
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

Many members have asked questions about increased risk of lung cancer among family members of people who have developed lung cancer. Overall, I have not highlighted this, partly because we don't tend to highlight genetics as a major contributor of lung cancer risk. But the fact is that 10-15% of people who develop lung cancer never smoked, and the vast majority of smokers never develop lung cancer. And we see that the never-smoker population with lung cancer is disproportionately female (as covered in a prior post), and that multiple surgical series of show much higher proportions of never-smokers with lung cancer in studies from China (57% never-smokers in article here), and Japan (48% never-smokers in article here). Genetics must be an important modifier, since some people chain smoke for decades without developing lung cancer, while others can develop lung cancer with no obvious risk factors.

First, there have been family clusters of lung cancer described in reports for several decades (abstract here). Since then, many reports have come out that suggest an increased risk of developing lung cancer for people with first-degree relatives with lung cancer (article here; abstract here). This appears to be independent of smoking exposure, which often overlaps with familial genetic traits. However, the familial genetic risk appears to be greatest among family members of never-smokers and those with adenocarcinomas (article here; another article here). There are many studies out there with a wide range of methods to assess risk, in a wide range of populations. Taken together, many of the studies in smokers show an increased risk in the 30-50% range, and the risk for relatives of never-smokers with lung cancer may be in the range of 6x normal. But it's important to consider that the risk of developing lung cancer for an individual person is still low, so it doesn't mean that a family member of someone with lung cancer is likely to get it as well.

What can we do with this information? Of course, if we could learn more about preventive approaches that may be effective, whether supplements or other interventions, we could target higher risk ppopulations for treatments to reduce risk. Unfortunately, we haven't identified any such approaches yet. There are a few screening studies that are enrolling people who may or may not have smoked but have a family history of lung cancer, so this designates them as higher risk even without the smoking history we're usually focusing on to estimate increased risk for smoking. But smoking status is still a very dominant factor, so my assessment would be that the most important point to take away from the increased risk of lung cancer among immediate family members of people with lung cancer is to reduce the risk by not smoking. If risk is going to be elevated, better to have that increase be for a very, very slight baseline risk. We can't control genetics, so most of what we can do is reduce the risks associated with behaviors that can be modified.

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