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Introduction to Lung Cancer in Never-Smokers
Dr Wakelee

The following is the edited transcript and figures from a webinar presentation made by Dr. Heather Wakelee, medical oncologist and Associate Professor at Stanford Cancer Center, on Never-Smokers and Gender Differences in Lung Cancer.

I'll start with the association of lung cancer with smoking.

tobacco-and-lc-death-rates (click on image to enlarge)

There is no doubt that smoking remains the biggest risk of lung cancer, and what this slide is showing in the green is cigarette consumption and how that started off in the 1900s, gradually increasing until the 1960s ,when the public first became aware of the health risks and as that dropped, lung cancer deaths also started to drop but obviously trailed that.

The gray line is the men, showing that men led early smoking cessation efforts and stopped, and so the death rates in men dropped as the cigarette smoking dropped. Unfortunately for women, we were a little slower to hear that message about health risks from smoking, and we're only now starting to see a tapering off of lung cancer in women. Still a little bit lower than men, but a real risk.

The slide above is looking at lung cancer incidence, which is the number of new cases. We have a lot of difficulty being able to figure out what percentage of people who have lung cancer have never smoked. The reason for that is that most of the data we have about lung cancer comes from cancer registries. Anytime anyone is diagnosed with a lung cancer, that information is sent to central registries. They're based around the country, but historically we've not been collecting smoking data in those, so we aren't able to really say exactly what percentage of people with lung cancer smoked or never smoked, or whether that changed over time. We can only infer that perhaps this is becoming a bigger problem with lung cancer and never smokers, but it remains difficult to get the data.

To try to answer that question I worked with several colleagues from one of the epidemiology resource centers in northern California. It use to be called the Northern California Cancer Center, and now the Cancer Prevention or CPIC Group of California and they're closely connected with Stanford as well as doing a lot of independent work.

What we did was we looked at multiple so-called cohort studies. These are studies where large groups of people, many thousands of people, are enrolled when they're healthy and then followed over time. During that time they ask a lot of questions on questionnaires about diet and smoking and other exposures. Then as time goes by certain people end up getting cancers or other health problems and then you can go back and look at all the data that was gathered over time to see what's different about the people who got cancer or whatever other problem versus everybody else.

Some of these are very famous. There's the California Teachers' Study, being run in California with the CPIC involved in that, and also the Nurses' Health Study, and many others. We were able to get information from these studies and look through to see who got lung cancer, and of the people who got lung cancer, how many didn't smoke and how many did smoke and try to put that together to get a better idea of what percentage of people with lung cancer haven't smoked, at least from this data.


In the figure above, this is looking at those patients from those big cohorts looking at everybody who got lung cancer. In "off white" it's the people who are current smokers, and so that's still the biggest risk. The magenta are the former smokers, and then the blue are the people who developed lung cancer who have never smoked.


The figure above blows up just the patients who have never smoked, and you can see that there's actually a sex difference. The women have higher rates than men, and this data is looking at incidence, or how many people get the lung cancer per 100,000 person-years. A person-year is one person being followed for one year, so 100,000 person-years is either a hundred thousand people being followed for a year, or fewer than that being followed over a longer period of time.

We can see that translated into an overall incidence rate of lung cancer in US women of that age range of 40-80 of just over 100 per 100,000 person-years. For never-smoking US women, it was about 20 per 100,000 person-years, so about a fifth of all of the lung cancer that we saw in these cohorts was in women who had never smoked. We see about 20% of women in the US with lung cancer have never smoked.

For men, that was about 10%, and that fits with what people have been guestimating for a while, around 15% overall, but we were showing the sex difference, and that's been shown by some other studies also.

That number of about 20 per 100,000 is actually comparable to cervical and thyroid cancer in US women in this age range -- so this entity of lung cancer in never-smokers is a large concern.

We continued looking at this question of lung cancer in nonsmokers focusing in the San Francisco area -- that's where I'm from -- and have this great resource with the epidemiologist at CPIC. There was also this is collaboration with investigators at UC-San Francisco where there was a study of all lung cancer patients diagnosed in the San Francisco Bay area over basically a decade, 1998 to 2008. There was a little interruption in 2004, but pretty much inclusive of that time, everybody who developed lung cancer during that time was contacted with an attempt to do a telephone interview. In those that were able to do a telephone interview or have a family member do that interview, we were able to determine their smoking history and a lot of other information about them as well as if they were born in the US, and this also included race and ethnicity, as well as social economic status.

Over this time period we were able to identify almost 3000 women who had developed lung cancer during that time period who also were available for a telephone interview. So obviously the total number was higher, but these were the people who could have a telephone interview. About 500, or about 20% were never smokers, about what we had estimated from those other cohort studies and with this being in the San Francisco Bay area, 94% of all of the patients were either Asian Pacific Islander, Hispanic, or other Non Hispanic Caucasian white women, a few were excluded for different reasons.

In total over this decade, within this small region, we found about almost 500 cases of women who had never smoked who developed lung cancer. Then we were able to look at the ethnicity of them and in this study of all the lung cancer cases in this study, the percentage of never smokers by racial ethnic group was pretty striking. Over 70% of the Asian Pacific Islander women who got lung cancer in our study were never smokers, about 35% of Hispanic women, and about 40% of non-Hispanic white women.

This is indicative that this is a disease that's a little bit different in each of the different ethnic groups, and there's been a lot of work, in Asia particularly, looking at this idea of lung cancer in never-smokers. There's been less work so far in the Latino patient population, and we're starting to look at that as are many others including investigators in Southern California.

NEXT: Why do never-smokers get lung cancer?

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