Is Lung Cancer Genetic?

In This Article

Although smoking remains the predominant cause of lung cancer in 80% to 90% of cases, genetics may play a part in some. It has been estimated that 8% of lung cancers are hereditary or occur as a result of a genetic predisposition. The risk of lung cancer may increase if a parent or sibling has the disease; even so, it doesn't mean that you will definitely get the disease if someone else in your family has it.

The current body of research suggests that genetics is more likely to contribute to the development of lung cancer if you are any of the following:

  • Younger (under age 50)
  • Female
  • A never-smoker

Although the science surrounding the genetics of lung cancer is still in its early years, scientists have identified certain mutations that may increase your risk.

lung adenocarcinoma symptoms
Illustration by JR Bee, Verywell

Influencing Factors

Familial lung cancer is a term that may suggest that a cancer gene is "passed" from parents to children. Today, researcher regard familial lung cancer as a combination of genetic and environmental factors that increase the risk of lung cancer among family members.

Overall, individuals with a first-degree relative (parent, sibling, or child) with lung cancer have an approximately 1.5-fold increased risk of the disease compared to those without a family history. This is true for both smokers and never-smokers.

But family history alone cannot predict if you will or will not get lung cancer. Your smoking status plays a more central role, wherein former or current smokers with a family history of lung cancer have no less than a three-fold increased risk of lung cancer compared to never-smokers without a family history.

Even so, a history of smoking will almost always contribute more to the development of lung cancer than genetics.

The current evidence suggests that the familial risk of lung cancer is influenced by multiple intersecting factors, including:

  • Genetics
  • Similar lifestyles (such as smoking and diet)
  • Similar environments (such as indoor and outdoor air pollution)

Secondhand smoke within the home, for example, can increase a person's risk of lung cancer by 20% to 30%. Similarly, radon exposure in the home—the second leading cause of lung cancer in the United States—may also factor into a person's familial risk of the disease.

As such, a family history of lung cancer cannot so much predict your likelihood of the disease as highlight the need to adjust modifiable risk factors and keep on heightened alert for any signs or symptoms of lung cancer.

Evidence of Genetic Risks

The science exploring the role of genetics in lung cancer is still young. Even so, there are a number of factors that suggest lung cancer has a hereditary component.

Younger Age

People who develop lung cancer at a younger age are more likely to have a genetic predisposition to the disease.

In the United States, the average age in which lung cancer is diagnosed is 70. Still, there are people who are diagnosed with lung cancer well before then. In fact, around 1.3% of all lung cancer cases occur in people under 35.

What is interesting about this younger population is that few are smokers, suggesting that other factors contribute to the risk. Genetics is believed to play a role in that almost all lung cancers in young adults are adenocarcinomas, a type of cancer closely linked to certain genetic mutations.

Sex

Men and women are about as equally likely to develop lung cancer. Still, there are disparities between the sexes.

Women are not only more likely to develop lung cancer at an earlier age than men, but they are also more likely to have it than male counterparts with the same risk factors.

According to a 2019 review in Translational Lung Cancer Research, women with a 40 pack-year history of smoking have a three-fold greater risk of lung cancer than men with the same smoking record.

Genetics is presumed to play a role, in part by increasing a woman's biological susceptibility to carcinogens (cancer-causing agents) in tobacco smoke.

Several studies have found that women have higher concentrations of an enzyme called CYP1A1, which can temper the body's response to carcinogens in the lungs and promote the development of cancer. Certain genetic polymorphisms (variations) are linked to the dysregulation of CYP1A1 production and may explain why women are more vulnerable to inhaled carcinogens.

Race

Race and ethnicity are also differentiating factors in the risk of lung cancer. Data from the ongoing Surveillance, Epidemiology, and End Results Program (SEER) notes that African Americans have a far greater risk of lung cancer than any other racial or ethnic group.

The SEER data provided the following the lung cancer incidence rates for the various groups (described in the number of cases per 100,000 people):

  • Blacks: 76.1 per 100,000
  • Whites: 69.7 per 100,000
  • Native Americans: 48.4 per 100,000
  • Asian/Pacific Islanders: 38.4 per 100,000
  • Hispanics: 37.3 per 100,000

Although things like smoking and the environment most certainly contribute to these rates, scientists have also noted that genetic mutations linked to lung cancer can also vary by race. Future studies hope to identify how significantly these mutations contribute to the risk in different races and ethnicities.

Hereditary Gene Mutations

Some types of lung cancer are more strongly linked to specific genetic mutations than others. These mutations can alter the function and life cycle of a cell, causing it to replicate abnormally and out of control, leading to the onset of cancer.

Scientists have identified certain genetic mutations associated with carcinogenesis (the development of cancer) in the lungs. The vast majority of these mutations are linked to non-small cell lung cancers (NSCLC), especially lung adenocarcinoma, as opposed to small cell lung cancers (SCLC).

Having a genetic mutation associated with lung cancer does not mean you will get lung cancer. Unlike BRCA mutations used to predict the likelihood of breast cancer in high-risk individuals, there is no genetic mutation or test that can predict the likelihood of lung cancer.

EGFR

Mutations of the EGFR gene can alter the production of a protein called epidermal growth factor receptor that helps cells respond appropriately to their environment. There are no less than 10 EGFR mutations known to be linked to lung cancer; many more are expected to be identified. 

Research suggests that 47% of Asians with NSCLC have an EGFR mutation. Around 21% of people with NSCLC who are of Middle-Eastern or African descent also carry the mutation; the same is true for 12% of patients who are of European descent.

EGFR mutations are also more common in women and non-smokers. While EGFR mutations are mainly linked to lung adenocarcinomas, some can affect squamous cell carcinomas by making them more aggressive.

EGFR mutations can be identified both in the primary (original) tumor and in metastases (secondary tumors that have spread to distant sites). These mutations tend to mutate rapidly and often become resistant to the drugs used to treat them.

KRAS

The KRAS gene is responsible for the production of a signaling protein called K-Ras that instruct cells on how to divide, mature, and function. Dysregulation of this protein can lead to cancer.

Around 15% to 20% of people with lung adenocarcinoma test positive for KRAS mutations. These often occur alongside EGFR mutations.

KRAS mutations are mainly identified in the primary tumor and less commonly in metastatic tumors.

ALK

The anaplastic lymphoma kinase (ALK) gene is responsible for the production of a protein called tyrosine kinase that instructs cells to divide and grow. The mutation, more accurately referred to as an ALK rearrangement, is linked to NSCLC and is more commonly seen in Asians than any other group.

ALK rearrangement is linked to between 3% and 5% of NSCLC cases (mainly adenocarcinomas) and is more commonly seen in light smokers, non-smokers, and people under 70.

BRCA2

It has been found that people with a BRCA2 gene mutation, one of the mutations associated with breast cancer, are at a higher risk of developing lung cancer as well.

This mutation is found in roughly 2% of people of European ancestry and is inherited in an autosomal dominant pattern (meaning that only one parent has to contribute the mutation to increase the risk of a disease).

Smokers who have a BRCA2 mutation are almost twice as likely to get lung cancer than the general population. By contrast, non-smokers with the BRCA mutation have a modestly increased risk.

Smokers carrying this mutation most often develop squamous cell carcinoma. Squamous cell carcinomas develop in the airways of the lungs, as opposed to adenocarcinomas that develop on the outer edges of the lungs.

Screening and Treatment

Scientists still have much to learn about the genetics of lung cancer. Although there are clear associations between lung cancer and EGFR, KRAS, ALK, and BRAS mutations, the identification of these mutations can in no way predict your risk of lung cancer. At this time, there are no recommendations regarding the genetic screening of people for lung cancer.

Where genetic testing can help is in the selection of newer targeted therapies in those already diagnosed with lung cancer. These drugs target and kill cancer cells with specific treatable mutations, leaving normal cells largely untouched. Because of this, targeted therapies often cause fewer side effects.

Among the targeted drugs used for NSCLC with an EGFR mutation:

  • Gilotrif (afatinib)
  • Iressa (gefitinib)
  • Tagrisso (osimertinib)
  • Tarceva (erlotinib)
  • Vizimpro (dacomitinib)

Among the targeted drugs used for NSCLC with an ALK rearrangement:

  • Alecensa (alectinib)
  • Alunbrig (brigatinib)
  • Lorbrena (lorlatinib)
  • Xalkori (crizotinib)
  • Zykadia (ceritinib)

A Word From Verywell

If you are at high risk for the disease, you may benefit from annual CT screening for lung cancer. Annual screening is currently recommended for people between the ages of 55 and 74 who smoke or have quit in the past 15 years and have at least a 30 pack-year history of smoking.

Depending upon additional risk factors, such as family history or radon exposure, you and your doctor may elect to choose screening outside of these parameters. Doing so may catch lung cancer early while it is still highly treatable.

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