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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.

Evidence of the Impact of Environmental Tobacco Smoke in Never-Smokers: Correlations with EGFR Mutations
Sat, 12/26/2009 - 06:04
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

It seems obvious: environmental tobacco smoke (ETS)/passive smoke exposure from being around smokers, can be harmful and may cause cancer in never-smokers. A new paper in the Journal of Clinical Oncology by Lee and colleagues from Korea actually offers some evidence that highlights this, showing that never-smokers in Korea were less likely to have an EGFR mutation if they were exposed to ETS.

Lee and colleagues from Korea assessed ETS in 179 consecutive never-smoking Korean patients with NSCLC by using trained interviewers who reviewed the number of smokers either living or working with a patient and the duration of their shared exposure. This led to a measurement of "smoker-years" that was the product of the number of smokers by the number of years living or working together (in their paper, the term "never-smoker" was actually assigned to those who not only never smoked personally but also had no significant direct exposure to smokers or tobacco.

Similar to the demographics of the famous IPASS trial of Asian never-smokers (or 6% light former smokers), the patient population skewed far younger than a typical lung cancer patient (58 in this study, vs. about 70 in broad populations) and was overwhelmingly female (>80%).

Though the proportion of patients they found with EGFR mutations was a little lower than was seen in the IPASS trial, (44% vs. 60%), the key finding was that patients with a history of ETS exposure were less likely to have a NSCLC tumor associated with an EGFR mutation than those with ETS exposure (38% vs. 61%), and there was a stepwise decrease in probability of having an EGFR mutation with gradually increasing ETS exposure. And the same pattern held true whether that exposure is in childhood or as an adult, at home or at work:

ets-and-egfr-mutation-rate(click on image to enlarge)

Sound familiar? As summarized in my recent post on why smoking status isn't as simple as "ever-smoker vs. never-smoker", that's essentially the exact same thing we've seen with direct tobacco exposure (from the patient smoking): while never-smokers have the highest probability of having an EGFR mutation, people with a minimal, remote smoking history have a greater chance of having an EGFR mutation than people who have smoked more and for longer. But now we see that this extends even into the range of people who have never-smoked.

Oncologists and other health care providers have not historically focused on obtaining a detailed smoking history, but now we're seeing mounting evidence that it may be relevant to know not only a person's personal smoking history -- in far more detail than just a yes/no question -- but also the history of their exposure to smokers.

The over-arching idea is that the EGFR mutation is a way that a single random genetic hit can lead to someone developing a lung cancer (or at least bringing someone a large part of the way there), while tobacco exposure leads to a complex collection of mutations that tend to not be amenable to dramatic responses by inhibiting a single key switch.

Of course, this also provides some evidence to corroborate the intuitive notion that smoking can not only increase risk for the smoker but for the people living and working around them. Perhaps this will provide even more incentive for a smoker to quit, knowing that it may well raise the risk of cancer in their spouse, child, co-workers, and other people close to them.

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