Risk factors for EGFR-positive lung cancer

Epidermal growth factor receptor (EGFR) is a protein on the surface of many cells, including cells in the lungs. It helps regulate how cells grow, divide, and survive.

In some types of cancer, EGFR becomes altered, most often through specific genetic mutations. These changes can cause the receptor to send out constant growth signals, leading to uncontrolled cell growth and helping tumor cells survive. Tumors with these changes are often classified as EGFR-positive.

In general, EGFR-positive lung cancer may have a better prognosis than other types of lung cancer. This is in part due to the availability of targeted therapies designed to block EGFR signaling and slow or stop tumor growth. Genetic testing is required to determine if a person has EGFR-positive lung cancer and whether they are eligible for these treatments.

EGFR-positive lung cancer can develop in anyone, but it is more common in some groups than others. This article explores groups with lung cancer who are more likely to have EGFR alteration and who may benefit from this targeted therapy.

EGFR alterations are most common in adenocarcinomas, the most common subtype of non-small cell lung cancer (NSCLC). Research estimates that anywhere from 10% to half of people with adenocarcinomas have EGFR-positive lung cancer, depending on their ancestry, age, and stage of disease.

Adenocarcinoma develops in glandular epithelial cells in the lungs, which tend to express higher levels of EGFR and depend more heavily on EGFR signaling for normal growth and tissue repair.

Smoking tobacco is the number one risk factor for lung cancer. It is responsible for an estimated 80% of lung cancer cases. However, about 12.5% of people who develop lung cancer have never smoked.

EGFR-positive lung cancer is more common among people who have never smoked or who have smoked very little. Research shows a significantly higher prevalence of EGFR mutations in non-smokers compared to those with any history of smoking.

Cancer develops when changes inside a cell allow it to grow and divide without the usual controls. In lung cancer, tumors in people who smoke often have a higher tumor mutational burden than tumors in people who have never smoked. This means they tend to carry more genetic changes overall, including many potential cancer-driving alterations.

In people have never smoked, lung cancer is more likely to be driven by one major mutation, such as an alteration in the EGFR gene, rather than a large number of mutations.

EGFR-positive lung cancer is more common in Asian populations than in other racial and ethnic groups. According to a review of 57 studies that included different lung cancer populations from around the world, EGFR alterations were found in about half of people with Asian ancestry, compared with about 12.5% of people with European ancestry.

Among Asian populations, EGFR-positive lung cancer is most common in those of East Asian descent. EGFR alterations are seen in about half of people with East Asian ancestry compared to one-third of people of South Asian ancestry.

EGFR-positive lung cancer is more common in females than in males. In one study of people with adenocarcinoma, about two-thirds of women had EGFR alterations compared to about one-third of men.

Researchers do not yet fully understand why EGFR alterations appear more frequently in females. However, sex-specific biological factors such as differences in hormone levels have been suggested as one possible explanation. Lifestyle factors may also contribute. For example, a higher proportion of women with lung cancer have never smoked compared to men.

For most people, EGFR mutations are not inherited. Instead, they develop during a person’s lifetime and can occur for a variety of reasons.

While EGFR-positive lung cancer can be diagnosed at any age, some research suggests it may be more common in younger adults, particularly those age 55 and under. One reason may be that EGFR-positive lung cancer can develop from a single “driver” mutation rather than requiring many years of toxin exposure, which is often the case with smoking-related cancers.

That said, research findings on age have been mixed, and consistent trends have not been identified across all populations. Differences in lifestyle factors, environmental exposures, and genetic ancestry may help explain why EGFR rates very between studies. In some cases, inherited genetic predispositions may also play a role.

Anyone can develop EGFR-positive lung cancer, but certain groups may have an increased likelihood for developing this specific cancer subtype.

Targeted treatments are available for people with EGFR alterations, and genetic testing can help determine eligibility. If someone in these high-risk groups for EGFR-positive lung cancer has not received genetic testing, it is important to discuss testing with their oncologist, as the results may help guide treatment decisions.