Lung Cancer Linked With Breast Cancer Gene (BRCA2)

DNA autoradiogram looking for BRCA2 mutations and an association with lung cancer


BRCA2 gene mutations are best known for how they increase the risk of developing breast cancer but may increase the risk of other cancers as well. One study found that women who carry a BRCA2 mutation and also smoke have twice the risk of developing lung cancer. Another study looking at a specific BRCA2 mutation (K3326) have twice the risk of developing small cell lung cancer, though this mutation only moderately raises the risk of breast cancer. Our knowledge of genetics and its relationship to cancer is still in its infancy, but extensive research now being conducted promises to clarify genetic risks for cancer in the future.

Let's look at BRCA2 mutations and lung cancer, how having these mutations increases risk, and when people might suspect they carry a mutation that increases their predisposition to cancer.

What Is a Genetic Predisposition?

Being born with a gene mutation such as BRCA2 doesn't mean that you will get cancer for sure. Instead, it means that you have an inherited susceptibility (genetic predisposition) or an increased likelihood of getting the disease. Depending on the specific gene mutation, your risk can vary considerably. For example, a mutation may mean that your chances of developing a disease are 80% or it could be very small.

Most of the time, the cause of cancer is considered to be multifactorial. This means that many (multiple) factors work together to cause or prevent a cancer. In the case of lung cancer, this could mean a combination of smoking, air pollution, radon exposure, or heredity increase your risk, while factors such as a healthy diet and exercise may reduce risk.

BRCA2 Gene Mutation and Cancer

The official name of the BRCA2 gene is the "breast cancer 2, early onset" gene. Mutations of the gene were first found to be associated with breast cancer, especially breast cancer in younger women.

Genes function by coding for proteins in the body, kind of like a blueprint. When BRCA genes are mutated, abnormal proteins are formed. The BRCA2 gene is a type of tumor suppressor gene. These genes code for proteins whose function is to repair damaged DNA (damaged as a result of environmental toxins, radiation, or mistakes in gene replication) or remove the cell via a process of programmed cell death termed apoptosis. Without this repair (or removal of the cell via apoptosis), the damage is allowed to go unchecked and cancerous cells may develop.

While some gene mutations affect a single protein, BRCA2 codes for a protein that works kind of like a manager. It's responsible for directing the actions of several genes that code for proteins whose function is to repair damaged DNA. Mutations in BRCA2 are not all the same, and researchers have found over 800 variants of the mutation.

How Common Are These Mutations?

Roughly 2% of people of European ancestry carry a BRCA2 mutation. This mutation occurs on chromosome 13 and can be inherited from either a mother or a father. Everyone carries two of these genes, and a mutation in only one confers risk.

This gene mutation is inherited in an autosomal dominant pattern meaning that if a parent carries a gene with the mutation, their children have a 50% chance of having the mutation. As noted above, having a BRCA2 mutation does not necessarily cause cancer, but increases the risk.

BRCA2 and Lung Cancer

There is an association between a specific BRCA2 gene mutation and lung cancer. In a study published in 2014, researchers looked at over 11,000 people with lung cancer and compared them to over 15,000 people without lung cancer. They found that smokers who carried a specific BRCA2 mutation were almost twice as likely to get lung cancer as smokers without the mutation.

What does this mean in numbers? People who smoke are 40 times more likely to develop lung cancer than those who do not smoke. Smokers carrying the mutation are roughly 80 times more likely to develop the disease. Describing this in another way: usually, 13 to 15% of people who smoke are expected to develop lung cancer, but for smokers who are positive for the BRCA2 gene mutation, their lifetime risk is roughly 25%. For never smokers, the risk of developing lung cancer for those who are positive for the specific BRCA2 gene mutation described in the study is slightly less than 2%.

BRCA2 gene mutations are most closely associated with squamous cell lung cancer, a form of non-small cell lung cancer.

BRCA Mutations and Small Cell Lung Cancer

Am unrelated 2018 study looked at the association of a very specific BRCA2 mutation and the occurrence of both lung cancer and a type of skin cancer. This particular mutation, BRCA2 K3326, a mutation referred to as a step-gene mutation, doubled the risk of developing small cell lung cancer but was associated with only a moderately increased risk of breast cancer. In addition to lung cancer, the mutation was associated with a risk of squamous cell skin cancer 1.69 times higher than those who did not carry the mutation.

Since BRCA genes are tumor suppressor genes, researchers theorized about what the differences in cancer risk occurred. It was thought that perhaps the proteins produced by the mutated BRCA2 genes may be able to continue to repair genes damaged by hormonal factors, but not by carcinogens in the environment.

Other Cancers Associated With BRCA2 Mutations

Several other cancers are associated with BRCA2 mutations. These include:

  1. Female breast cancer: For women who have a BRCA2 mutation, 45% will develop breast cancer by the age of 70
  2. Male breast cancer
  3. Ovarian cancer: 11 to 17% of women with this mutation will develop ovarian cancer (ordinarily 1.4% of women)
  4. Pancreatic cancer
  5. Fallopian tube cancer
  6. Melanoma
  7. Peritoneal cancer
  8. Prostate cancer
  9. Laryngeal cancer

How to Know If You Carry a Mutation

At the current time, most people who carry a BRCA2 mutation are completely unaware. Having a family history of breast cancer, especially if it has occurred in several members or at a young age, increases the likelihood.

The mutation has been found to be more common in certain ethnic groups including Ashkenazi Jews and peoples of Norwegian, Dutch, and Icelandic ancestry.

The Future

In the future, drugs may become available for people with lung cancer harboring this mutation. While they have not been tried with lung cancer, medications known as PARP inhibitors have been somewhat successful in clinical trials involving people with breast cancer and ovarian cancer with BRCA2 mutations.

A Word From Verywell

We are just beginning to learn that some specific gene mutations are associated with an elevated risk of lung cancer, but there are several important points to keep in mind.

  1. It's important to remember that a predisposition does not mean you will get cancer. Maintaining a healthy lifestyle, eating healthily and exercising may lower your risk.
  2. Take a good family medical history and encourage other family members to do so as well. This may reveal a predisposition to cancer as well as other conditions such as heart disease. Depending upon your family history your doctor may choose to monitor you more closely or at an earlier age for these conditions. Keep in mind that some conditions had different names in times past, for example, "dropsy" for the swelling associated with heart failure.
  3. If you smoke, quit, whether or not you have a BRCA2 gene mutation.
  4. For people who are at high risk, talk to your doctor about the option of lung cancer screening.
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