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New study aims to identify lung cancer risk in nonsmokers

Updated March 27, 2024: Since this article was originally published, the recruitment time period was extended to five years. The study is currently actively recruiting participants. Please go here for more details.
“Anybody with lungs can get lung cancer.”
It’s not a flippant remark. Or an exaggeration.
They are the words of a 35-year-old Southern California mother of two who was treated at City of Hope for Stage 4 lung cancer. Healthy, active and “in the best shape of my life,” the diagnosis shocked her. She had never smoked.
She’s far from alone.
While smokers — past and present — still account for the overwhelming majority of lung cancer cases, each year tens of thousands of Americans who never picked up a cigarette get the news they never expected to hear. There is also evidence that the proportion of so-called “never-smokers” with lung cancer is growing.
“We know that lung cancer in nonsmokers is a significant public health problem,” said Stacy W. Gray, M.D., chief of City of Hope’s Division of Clinical Cancer Genomics. “Sadly, though, the risk factors [for this group] are not well understood.”
Worse, while the Centers for Disease Control and Prevention urges smokers to get annual cancer screenings — usually a computed tomography (CT) scan — to detect cancer as early as possible, nonsmokers have no such mechanism, as the CDC starkly states:
“The U.S. Preventive Services Task Force does not recommend lung cancer screening for people who have never smoked...because the possible harms of screening outweigh the possible benefit in this group.”
Stacy Gray

Stacy Gray, M.D.

Those “harms” include risks associated with the low-dose radiation generated by the CT machine, as well as the possibility of false positives prompting more invasive procedures, like biopsies, to confirm the presence of cancer.

As a result, most nonsmokers don’t get screened, which means they do not have the option to use a critical early-detection tool. Those who do develop lung cancer are more likely to be diagnosed at a later stage, limiting their treatment options and lowering survival rates.
“There are too many people getting lung cancer who were not eligible for screening,” laments surgeon and researcher Dan J. Raz, M.D., co-director of the Lung Cancer and Thoracic Oncology Program. “We need to find an option for them.”
Gray and Raz are leading a new effort to change that reality. They’ve undertaken a first-of-its-kind study that looks exclusively at nonsmokers who have “identifiable non-tobacco-related risk factors for lung cancer,” such as family history and certain DNA mutations. Half the participants have been diagnosed with lung cancer; the other half are cancer free. By evaluating the two groups, researchers hope to learn several things:
1. Is It in the Genes? Exactly how do genetic anomalies figure in the development of lung cancer? Collecting this data may shed more light on this still-in-its-infancy area.
2. Scan for Abnormalities. By administering low-dose CT scans to participants without cancer, it is hoped that patterns will emerge — detection of any abnormal findings — that will help set standards for accurately screening nonsmokers in the future.
3. Check the Neighborhood: Many external factors may contribute to lung cancer: everything from environmental challenges, such as air pollution, secondhand smoke and radon, to broader factors, such as socioeconomic status, neighborhood safety, food insecurity and access to proper health care; the so-called “social determinants.” The study will attempt to quantify those factors through medical records and patient questionnaires. “We’ve studied cancer too long without asking these questions,” said Gray. “We’re trying to connect the dots.”
4. Liquid Biopsy. Blood tests that reveal circulating cancer cells or DNA fragments can be a powerful tool to detect lung cancer in its earliest stages, even before anything shows up on a CT scan. Nonsmokers, however, have different mutations and genetic alterations than smokers with lung cancer, so it’s necessary to accumulate more data to see how well liquid biopsies will perform in this patient population.
It’s the liquid biopsy element that most excites Raz, a strong advocate of increasing lung cancer screenings whenever possible.
Doctor Dan Raz

Dan Raz, M.D.

“All previous liquid biopsy studies for lung cancer were designed for smokers,” said Raz. “So for non-smokers, we need to make sure the test will be accurate.” Right now, some studies have shown that liquid biopsies can be 95-100% accurate in detecting cancer, but considerably less precise — about 60-85% — in confirming the absence of cancer. Raz is optimistic. “It’s definitely the wave of the future. The technology will get better and better.”

No one has any illusions that this preliminary effort by itself will bring about fundamental changes, given its small size: 200 participants over a two-year period. Rather, it is seen as a first step and perhaps a template.
“It’s a pilot study,” explained Gray, “to help us understand what we’ll need in future studies, to see if lung cancer in nonsmokers can be caught early, if liquid biopsies can help us do it, and whether we can see a pattern in those social factors.”
“Success in this study,” added Raz, “will be that we’re able to collect all the data we hope to collect, then use it to build additional studies.”
The longer term goal is obvious.
Women above a certain age, regardless of family history, are urged to get mammograms to detect breast cancer. Men are told to get a PSA test to look for prostate cancer. Other patients are offered “high risk” screening or prevention measures after using, as Gray notes, “sophisticated, personalized methods of risk stratification”  that take into account a patient’s past medical history, family history and other risk factors.
But preventing lung cancer among the large, nonsmoking population has never received this kind of attention, probably because the “800-pound gorilla” — cigarette smoking — has dominated most discussions and research, not to mention most lung cancer funding. Gray and her team want the same tools routinely accessed by smokers to be available to anyone at high risk.
“Our goal is to detect lung cancer as early as possible,” she said. “Or prevent it.”