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Dr West

Genetics, Family History, and Lung Cancer

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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.


12 Responses to Genetics, Family History, and Lung Cancer

  • Linda says:

    I was wondering if different location of adenocarcinomas run in families with a smoking hx – my mom had early stage bowel cancer-adenocarcinoma (smoked in late 20’s early 30’s-dx at age 65 with no problems since (71). My uncle (her brother) passed away at age 57 from bone cancer which had apparently spread from questionable location. The details are sketchy; however, I was told that it was adenocarcinoma. He smoked for many, many years and had health issues related to back pain, etc for several years prior to his death. Of course, I smoked as well (quit 15 years ago) and my lung cancer was a subset of adenocarcinoma.

    Both my sisters (42/51) have quit smoking in the last year or so and I am concerned about their risk factors (more so than my own young children as they have never been exposed to cigarette smoke-although there is certainly no guarantee they will be safe either!). Both sisters had a CXR after my diagnosis last year; however, I am wondering if they wouldn’t benefit from a CT scan. Could there be something in our gene pool that makes this type of cancer risk higher for our family? I hope I don’t sound stupid asking this question; however, I have wondered and worried about this possibility. I know there are no clear cut answers on this issue – my biggest question is whether you feel my siblings would benefit from a baseline CT scan?

    Thanks once again – your posts are always informative.

  • Dr West
    Dr. West says:

    The literature on this subject is pretty varied. Yes, there are some studies that show increased risks among family members with lung cancer, and not all are restricted to increased risk of a lung cancer. In particular, several of the studies of never-smokers with lung cancer have reported on the potential for increased risks of various cancers. However, the studies are all different, with no highly consistent findings that give a clear answer to these questions. I’m pretty sure I could find a trial or two results to support just about any idea I’d want to put out there.

    As for your question about screening, it’s tough, because we still haven’t reached a consensus about the value of screening in smokers, so CT screening based on family history is even more frought with questions. I can’t say I’d go as far as to recommend screening, but I’d be very supportive of participating in any screening study that enrolled patients based on family history and for which your sibs would be eligible. That’s a bit of a cop-out, but I just don’t have a clear answer to such a tough question.

    -Dr. West

  • jlenzmeier says:

    Dr. West,

    Do you know where a person could enroll in a screening study based on family history?

  • blaze100 says:

    Hi Dr. West, Four of my cousins have the alpha 1 antitrypsin deficiency.

    Is there possible connection with BAC?

    Barb

  • Dr West
    Dr. West says:

    Not that I’m aware of.

  • Karen says:

    Hello,
    I do feel that Genetics play a HUGE part in all cancer, including Lung. My husband has lung cancer at 34, his both aunts had it, one smoked one non smoker, and his grandmother there mother had it too, cervical and small cell throat. I think it runs in families genes like breast cancer, heart disease. Etc.

  • Dr West
    Dr. West says:

    Karen, and others,

    Genetics plays a part in many cancers, but an additional point (not either/or) is that cancer is very common in general, like heart disease, high blood pressure, diabetes, and many other medical problems. Cancer is the second leading cause of death in the US, behind heart disease, and as we’ve made major strides in dealing with heart disease, more people live long enough to get cancer. Cancer is largely age-related: over time, the cells of the body have been dividing and accumulate mutations from bad copies over decades, and with time some cells collect the right (or wrong) combination of enough mutations to become cancerous. So as more people live longer, cancer rates go up, because that’s a by-product of aging. Which is not to say that genetics isn’t an issue, especially when cancer affects younger people, but families are more remarkable if they don’t have any history of cancer than if they do, because it’s just very common in the population.

    -Dr. West

  • Karen says:

    Thank you Dr. West,
    I do understand. What makes me angry is people look at LC as something that the patient did to themselves, and that is not always the case, some do not smoke and get it from being hero’s in 911 rescue’s, some get it from the genetics etc. not all get it from smoking, it is unfair of the lack of funding for the type of cancer compared to others, becuase it is because of smoking, it is not always because of that, but I know what you are saying too.
    have a great day!

  • Dr West
    Dr. West says:

    I agree. Nobody deserves lung cancer, but the world needs to understand that there are many factors and that it doesn’t boil down to deciding to smoke. Plus, many people feel compelled to continue to smoke and, after developing the addiction/habit, don’t feel that they have much choice in the matter.

    -Dr. West

  • slcougar says:

    I’m a male 56 year-old never-smoker with stage IV NSCLC adenocarcinoma currently undergoing clinical trial chemo treatment @ UC Davis is Sacramento. I would like answers to the following:
    1) Why has there not been a comprehensive survey of all people diagnosis with primary lung cancers that would include backgorund information on diet, living location, exercise habits, family history, etc., similar to the one done in the book “The China Study” by the Campbells?
    2) How can we get this survey done so the data can be evaluated to assist in identifying possible causes and/or risk factors?

    I was told when I first started treatments that they do not know the cause of my disease, but suspect it is something “environmental”? We must narrow this broad reply down by gathering and studying data from patients.

  • dabarger says:

    Interesting thread. A quick rundown of my own family history :My Great grand mother (father’s side) died of stomach cancer. Father is a colon cancer survivor. One nephew that is a skin cancer survivor.One brother that died of nsclc after being staged at 3a. I’m currently in remission from stage 3b nsclc. So far I have undergone the same treatment as my brother. carbo/taxol concurrently with radiation. My father,I are both former smokers as was also a smoker.I have also worked in the pest control industry (3 years) and over 10 years in plastics manufacturing.

    As for screening, I had 2 chest x rays in Nov. 06 both were interpreted as bronchitis. Three weeks after the second x ray,I had ct scan and was ultimately staged at 3b T4N3, squamous cell nsclc.I have another brother (never smoker) and a sister (former smoker) who both insisted on and were screened by CT. Both were negative.

    Based on my own family history it would appear that genetics does play an important role. But there is also evidence to suggest other environmental factors may have been in play in my case at least.

    While the jury may still be out concerning x ray versus ct scan, from my own experience it would seem that at least those folks who may be considered high risk be screened using ct scan.

    Interesting thread!

    David Barger

  • Dr West
    Dr. West says:

    slcougar,

    Practically speaking, it’s unfathomably complex and extraordinarily expensive. There are more than 170,000 new cases of lung cancer in the US alone, and doing detailed studies of everything they’ve ever been exposed to, plus integrating genetic research, which would obviously be involved, would cost more than we could even consider spending when federal research funds are being severely limited. Most of the research in cancer in the US at this time is sponsored by pharmaceutical companies, and the questions you’re asking don’t lead to answers that could justify their investment. I don’t mean to say it’s not worth knowing, but this is incredibly expensive, and even if we had all of the data, there are so many variables (food, chemicals, smoking history, location, genetics, lots more) that we still may not end up with most of the answers.

    David,

    I’m sorry for what you’re facing, as well as your whole family.

    There are clearly many things we still need to learn about risk factors for lung cancer, especially genetics/family history. Tomorrow I’m seeing a new 41 year old female never-smoking Taiwanese woman who was urged to get screened by her father, after her mother developed metastatic NSCLC as a never-smoker. She had a stage IA NSCLC, resected, and is now seeing me to consider if there’s anything to be done to try to reduce risk in the future (my answer is nothing that we know of, I’m afraid). We see many cases that illustrate how central genetics are in risk for developing lung cancer.

    -Dr. West

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