Is Lung Cancer Genetic?

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Although smoking remains the predominant cause of lung cancer, responsible for 80% to 90% of all lung cancer cases, heredity may contribute to lung cancer in some instances. It has been estimated that 8% of lung cancers are linked to a genetic predisposition. The risk of lung cancer may increase if a parent or sibling has the disease; even so, it doesn't mean you will definitely get the disease if someone in your family has it.

The current body of research suggests genetics is more likely to contribute to lung cancer for people who are:

  • Young (under age 50)
  • Female
  • Never-smokers

Scientists have identified certain genetic mutations (alterations in your genetic code) that may increase your risk of lung cancer. But this doesn't mean that all genetic mutations associated with lung cancer are inherited. You can inherit genetic mutations, or you can acquire these changes at any time during your life due to environmental factors (such as due to smoking or pollution).

lung adenocarcinoma symptoms
Illustration by JR Bee, Verywell

Influencing Factors

Family history alone cannot predict if you will or will not get lung cancer. Familial lung cancer is a term that may suggest that a cancer gene is "passed" from parents to children.

Today, researchers 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.

A history of smoking will almost always contribute more substantially to the risk of lung cancer than an inherited predisposition to the disease.

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

  • Heredity
  • 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

There are a number of factors suggesting a small hereditary component when it comes to the risk of lung cancer.

Younger Age

In the United States, the average age at 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, which raises questions about which other factors might contribute to the risk. People who develop lung cancer at a younger age are more likely to have genetic changes associated with the disease.

But a hereditary link to these genetic changes has not been established.

Almost all lung cancers in young adults are adenocarcinomas, a type of cancer closely linked to certain acquired (not inherited) genetic mutations.

Sex

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

Females are not only more likely to develop lung cancer at an earlier age than males, 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, females with a 40 pack-year history of smoking have a three-fold greater risk of lung cancer than males with the same smoking record.

Genetic or hormonal factors may play a role, possibly by increasing a female's biological susceptibility to carcinogens (cancer-causing agents) in tobacco smoke.

Several studies have found that females 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 females 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 lung cancer incidence rates for 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 may identify how significantly these mutations contribute to the risk among different races and ethnicities, and whether genetic mutations are inherited or acquired.

Gene Mutations

Some types of lung cancer are more strongly linked to specific genetic mutations than others, but they have not been established as inherited. In fact, they are believed to be acquired. 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 fewer 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 instructs 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 type of tyrosine kinase protein 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 BRAF mutations, these mutations are believed to be acquired and they are only found in the cancer cells, not in other cells of the body. So they can't be identified before lung cancer develops (but certain inherited mutations such as BRCA1 and BRCA2 can be identified in advance).

At this time, there are no recommendations regarding genetic screening for lung cancer. Research investigations aimed at identifying inherited genes that lead to or predispose to lung cancer are still not yielding definitive information.

Where genetic testing can help is in the selection of targeted therapies for the treatment of lung cancer. With this type of approach, lung cancer tissue is tested for genetic mutations, and cancer treatment that specifically destroys cancer cells that have the identified gene mutation can be used.

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 50 and 80 who have at least a 20 pack-year history of smoking. Some guidelines limit screening to those who smoke or have quit in the past 15 years, while others don't.

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

24 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Alberg AJ, Brock MV, Ford JG, et al. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e1S-e29S. doi:10.1378/chest.12-2345

  2. Kanwal M, Ding XJ, Cao Y. Familial risk for lung cancer. Oncol Letters. 2017;13(2):535-42. doi:10.3892/ol.2016.5518

  3. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863-70. doi:10.1200/JCO.2011.35.6345

  4. Coté ML, Liu M, Bonassi S, et al. Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium. Eur J Cancer. 2012;48(13):1957-68. doi:10.1016/j.ejca.2012.01.038

  5. Environmental Protection Agency. Indoor air quality (AIQ).

  6. American Cancer Society. Lung cancer statistics.

  7. Liu B, Quan X, Xu C, et al. Lung cancer in young adults aged 35 years or younger: A full-scale analysis and reviewJ Cancer. 2019;10(15):3553-9. doi:10.7150/jca.27490

  8. Hellyer JA, Patel MI. Sex disparities in lung cancer incidence: Validation of a long-observed trend. Transl Lung Cancer Res. 2019;8(4):543-5. doi:10.21037/tlcr.2019.04.06

  9. Penaloza CG, Estevez B, Han DM, Norouzi M, Lockshin RA, Zakeri Z. Sex-dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA. FASEB J. 2014;28(2):966-77. doi:10.1096/fj.13-233320

  10. National Cancer Institute/Surveillance, Epidemiology, and End Results (SEER) Program. SEER cancer statistics review (CSR) 1975-2017.

  11. Schabath MB, Cress D, Munoz-Antonia T. Racial and ethnic differences in the epidemiology and genomics of lung cancer. Cancer Control. 2016;23(4):338-46. doi:10.1177/107327481602300405

  12. Gaughan EM, Cryer SK, Yeap BY, Jackman DM, Costa DB. Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations. Lung Cancer. 2013. 79(3):193-7. doi:10.1016/j.lungcan.2012.12.002

  13. Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol. 2020;61:167-79. doi:10.1016/j.semcancer.2019.09.015

  14. Benbrahim Z, Antonia T, Mellas N. EGFR mutation frequency in Middle East and African non-small cell lung cancer patients: a systematic review and meta-analysisBMC Cancer. 2018;18(1):891. doi:10.1186/s12885-018-4774-y

  15. Joshi A, Zanwar S, Noronha V, et al. Mutation in squamous cell carcinoma of the lung: Does it carry the same connotation as in adenocarcinomas?. Onco Targets Ther. 2017;10:1859-63. doi:10.2147/OTT.S125397

  16. Ma C, Wei S, Song Y. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis. 2011;3(1):10-8. doi:10.3978/j.issn.2072-1439.2010.12.02

  17. El-Telbany A, Ma PC. Cancer genes in lung cancer: racial disparities: are there any?. Genes Cancer. 2012;3(7-8):467-80. doi:10.1177/1947601912465177

  18. Du X, Shao Y, Qin HF, Tai YH, Gao HJ. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer. 2018;9(4):423-30. doi:10.1111/1759-7714.12613

  19. Lee YC, Lee YC, Li CY, Lee YL, Chen BL. BRCA1 and BRCA2 gene mutations and lung cancer risk: A meta-analysis. Medicina (Kaunas). 2020;56(5):212. doi:10.3390/medicina56050212

  20. Yamamoto H, Yatabe Y, Toyooka S. Inherited lung cancer syndromes targeting never smokers. Transl Lung Cancer Res. 2018;7(4):498-504. doi:10.21037/tlcr.2018.06.01

  21. de Alencar VTL, Formiga MN, de Lima VCC. Inherited lung cancer: a review. Ecancermedicalscience. 2020 Jan 29;14:1008. doi: 10.3332/ecancer.2020.1008. PMID: 32104210; PMCID: PMC7039693.

  22. American Cancer Society. Targeted drug therapy for non-small cell lung cancer.

  23. Wolf AMD, Oeffinger KC, Shih TY, et al. Screening for lung cancer: 2023 guideline update from the American Cancer Society. CA Cancer J Clin. 2023;10.3322/caac.21811. doi:10.3322/caac.21811

  24. US Preventive Services Task Force. Screening for Lung Cancer: US Preventive Services Task Force Recommendation StatementJAMA. 2021;325(10):962–970. doi:10.1001/jama.2021.1117

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."