Can Lung Cancer Be Detected Early via Blood Test in Never-Smokers? CEACAM5 and CEACAM6 in a JAMA Study

The Silent Lung Cancer Risk in People Who Have Never Smoked: What Do CEACAM5 and CEACAM6 in the Blood Reveal?

Lung cancer is usually linked with smoking, yet roughly one in every four to five people with lung cancer has never smoked, and for this group there is currently no accepted method of early detection. A study published in JAMA Network Open on November 2, 2026, led by the International Agency for Research on Cancer (IARC), part of the World Health Organization, compared blood samples taken years before diagnosis from 180 never smokers with lung cancer against samples from 180 matched healthy people. Of the 2,821 proteins examined, only two, CEACAM5 and CEACAM6, were significantly associated with later developing lung cancer. In this article we explain what the study found, what it did not find, and what never smokers can do today. An important note: this study does not yet provide a ready-to-use blood test or screening method. We covered the general symptoms of lung cancer in our lung cancer guide and screening for people who smoke in our article on screening recommendations.

Why does this matter?

Considered on its own, lung cancer in never smokers is the fifth leading cause of cancer-related loss of life worldwide. Most of these cancers are adenocarcinomas; according to 2022 data, 53–70% of lung cancers in never smokers are of this type, and about 15% have been linked to air pollution. They are more common among women and people of East Asian descent, and genetic changes that can be treated with targeted drugs, such as EGFR, are also more frequent in this group (lung cancer in women, EGFR-mutated lung cancer).

The problem is this: screening with low-dose computed tomography (CT) is recommended only for people with a heavy smoking history. Never smokers fall outside these programs, and their cancers are often found only after symptoms appear, at an advanced stage (screening in people who smoke). That is why the idea of a simple blood test that could pick out the higher-risk never smokers is so appealing. But there is a long road from discovering a biomarker to putting it into use, and not every promising result makes it to the end of that road (how to read research news).

Can a blood test detect lung cancer early in never smokers?

Not yet. A study published in November 2026 showed that higher blood levels of the proteins CEACAM5 and CEACAM6 in never smokers were associated with the risk of developing lung cancer within 5 years. However, these findings have not been confirmed in large groups of never smokers, and no blood test that can be used for screening or diagnosis exists today.

Why does lung cancer develop in people who don't smoke?

In never smokers, lung cancer behaves like a different disease from the one seen in smokers. The tumors are mostly adenocarcinomas, carry fewer mutations and more often depend on a single "driver" change such as EGFR, ALK or ROS1 (ALK-positive lung cancer). Risk factors include air pollution, radon gas, secondhand smoke, indoor cooking and fuel smoke, occupational exposures such as asbestos, and a family history of lung cancer. In many patients, however, no clear cause can be found (smoking and cancer, facts about lung cancer).

How was the study done?

The researchers drew on four large studies in the Lung Cancer Cohort Consortium (LC3): the Cancer Prevention Study II and the Multiethnic Cohort in the US, and the Shanghai Men's and Women's Health Studies in China. In these studies, blood was collected from tens of thousands of people between 1996 and 2010, and the samples were stored frozen. The team identified 180 never smokers who were diagnosed with lung cancer within 5 years after their blood was drawn. Each was matched with a person from the same cohort, of the same age and sex, who had given blood at the same time and did not develop cancer. Of the participants, 71% were women and 82% were of Asian descent, and the median age was 66.

In the stored blood samples, 2,821 different proteins were measured at the same time using a research platform called Olink Explore 3072. When so many proteins are examined, some associations will inevitably appear by chance, so the researchers applied a multiple-comparison correction. After this correction, only two proteins remained significant: CEACAM5 and CEACAM6. The findings were then tested in an independent group in the UK Biobank in Britain, which included 49,291 people and 157 lung cancer cases (multiple analyses from a single blood sample, blood transcriptome atlas).

Results: how strong is the association?

In people whose blood level was one standard deviation higher (roughly "clearly above average"), the odds of lung cancer were 1.65-fold higher for CEACAM5 and 1.72-fold higher for CEACAM6. In the UK Biobank, across all participants, smokers and never smokers alike, the association was even stronger (1.92- and 1.86-fold). But when only never smokers in the UK Biobank were considered, the number of patients fell to 16; the association remained significant for CEACAM5 (1.84-fold), whereas for CEACAM6 it was not significant because the confidence interval included 1.

The association weakened somewhat as the time between blood draw and diagnosis grew longer, but it did not disappear: both proteins were also significantly elevated in blood drawn 2.5–5 years before diagnosis. This suggests that the proteins may reflect not only a tumor that is already present but not yet noticed, but also a risk that will develop later. The association was seen in squamous cell and small cell lung cancer as well as in adenocarcinoma.

What are CEACAM5 and CEACAM6?

CEACAM5 and CEACAM6 belong to the family of carcinoembryonic antigen-related cell adhesion molecules. They help cells attach to one another and to their surroundings, and they are normally present in small amounts on some epithelial cells. When cells begin to turn cancerous, the amount of these proteins on their surface can increase and some of it passes into the blood. CEACAM5 is, in fact, the very CEA tumor marker that has been in use for decades (what is the CEA test?).

An important caution is needed here: the CEA blood test is widely available, including in Türkiye, but it is not recommended for cancer screening in healthy people. CEA can rise in smokers, with liver and bowel inflammation and in many other conditions, while it stays normal in most early-stage cancers. The research platform used in this study is also not the same as the CEA test in clinical laboratories, and the results cannot be converted directly from one to the other. For this reason, conclusions such as "My CEA is a little high, could I have lung cancer?" or "My CEA is normal, so I don't have lung cancer" cannot be drawn from this study.

A different biology in people who don't smoke

Perhaps the most interesting finding of the study was that most of the 36 proteins previously shown to predict lung cancer risk in smokers were of no use in never smokers. The median odds ratio for these proteins was 1.47 in smokers but 1.01 in never smokers, in other words, practically "no effect." Only CEACAM5, ALPP, SPINT1 and WFDC2 showed an association in the same direction in both groups. This suggests that lung cancer in never smokers has a biology of its own and that risk tools developed for smokers cannot be applied directly to this group (tumor genetics and NGS).

Limitations of the study

Screening in never smokers: today and tomorrow

Today, US and European guidelines recommend low-dose CT screening only for people in a certain age range with a heavy smoking history. There is no routine screening recommendation for never smokers. The most notable experience here comes from Taiwan: in the TALENT study, 12,011 people, 93% of whom had never smoked and half of whom had a family history of lung cancer, were screened with low-dose CT; lung cancer was found in 2.6%, and 96.5% of these cancers were stage 0 or I. Based on these results, Taiwan added people with a family history of lung cancer to its national screening program. However, the effect of this kind of screening on survival, and harms such as unnecessary biopsies, are not yet clear (what is a lung nodule?).

The possible role of blood markers such as CEACAM5 and CEACAM6 here is to help decide who should be screened with CT. In other words, a blood test would not diagnose cancer on its own, but it could make screening more efficient by picking out those at higher risk. Similar "early detection from blood" approaches are being studied in colon and pancreatic cancer, and some have reached the approval stage (multi-cancer blood test, blood test for pancreatic cancer, blood test for colon cancer).

What should a never smoker do today?

Screening with a blood test is not yet possible, but reducing risk factors and recognizing symptoms are the most effective steps you can take today. If you have a cough lasting more than three weeks, are coughing up blood, or have shortness of breath, chest pain, hoarseness or unexplained weight loss, the fact that you don't smoke does not rule out lung cancer completely; you should see a doctor (coughing up blood).

The situation in Türkiye

Questions to ask your doctor

• I have never smoked, but lung cancer runs in my family. Could low-dose CT be considered for me?
• Do I need a chest X-ray or CT for my cough that won't go away?
• Is there an exposure at my home or workplace that raises my lung cancer risk?
• My CEA test came back high; does that mean lung cancer?
• If I am diagnosed with lung cancer, will genetic tests such as EGFR be done?

Frequently Asked Questions

Can a blood test detect lung cancer early in never smokers?

Not yet. A study published in November 2026 showed that higher blood levels of CEACAM5 and CEACAM6 in never smokers were associated with lung cancer risk within 5 years. However, these findings have not been confirmed in large groups, and there is no ready-to-use test.

What are CEACAM5 and CEACAM6?

They are surface proteins that help cells attach to one another. They can increase in cells that are turning cancerous and pass into the blood. CEACAM5 is the very CEA tumor marker that has been used for decades; however, the CEA test is not suitable for screening.

What causes lung cancer in never smokers?

The main risk factors are air pollution, radon gas, secondhand smoke, indoor cooking and fuel smoke, occupational exposures such as asbestos, and a family history of lung cancer. In many patients no clear cause can be found.

Should never smokers get lung cancer screening?

Today there is no routine screening recommendation for never smokers. People with a family history of lung cancer or with symptoms should talk to their doctor. In Taiwan, people with a family history of lung cancer are screened with low-dose CT.

Glossary

Biomarker

A measurable characteristic that indicates the presence, risk or course of a disease.

CEA (CEACAM5)

Carcinoembryonic antigen; a protein that can rise in the blood in some cancers and is used to monitor treatment.

CEACAM6

Another surface protein from the CEA family that plays a role in cell adhesion.

Nested case-control study

A study in which people in a large follow-up group who later develop a disease are compared with matched healthy people using stored samples.

Odds ratio (OR)

A measure of how many times higher the odds of a disease are in people with a characteristic than in those without it; 1 means no difference.

Confidence interval

The range that very likely contains the true value; if it includes 1, the association is not significant.

Relative and absolute risk

Relative risk shows how many times the risk increases; absolute risk shows a person's actual chance of developing the disease.

Low-dose CT

Computed tomography with low radiation, used in lung screening.

Adenocarcinoma

The most common type of lung cancer; also the most common type in never smokers.

Radon

A colorless, odorless radioactive gas that seeps from the ground and can build up indoors.