BRCA1 And BRCA2 Genetic Markers And Breast Cancer Risk

The BRCA Genes

The name “BRCA” is an abbreviation for the “BReast CAncer gene.” BRCA1 and BRCA2 are two different genes found to impact a person’s chances of developing breast cancer.

Despite what their names might suggest, BRCA genes do not cause breast cancer. These genes normally play a big role in preventing breast cancer.

The BRCA genes carry instructions for the production of proteins that are responsible for preventing uncontrolled cell growth. These proteins are called tumor suppressor proteins. If these proteins do not function properly, it results in the uncontrollable growth of cells, which may end up being cancerous.

The BRCA proteins also help repair damaged DNA, thereby maintaining the stability of genetic information. DNA damage can occur due to errors during the DNA replication process or by environmental agents like UV or ionizing radiation.

BRCA?Gene Mutations

Certain changes or mutations in the?BRCA?genes prevent the proteins from doing their job properly and may lead to uncontrolled cell division, increasing a person’s risk of developing cancer. These genetic changes are called harmful or pathogenic variants.

Not all cancers are inherited, but a person carrying a change in the?BRCA1?or?BRCA2?gene can pass it on to their children and increase their lifetime risk of developing cancer. If either your mother or father has a?BRCA1?or?BRCA2?gene mutation, you have a 50% chance of having the same gene mutation.

About 1 in every 500 women in the United States has a mutation in either her?BRCA1?or?BRCA2?gene.

BRCA?Mutations and Breast Cancer Risk

Inherited mutations in the?BRCA1?gene are responsible for about 40-45% of hereditary breast cancers.

BRCA2?germline mutations, which are mutations inherited from either parent, are seen in?approximately 35% of families with incidences of early-onset breast cancer in their women.

According to the National Cancer Institute, NIH,?55-72%?of women who inherit a harmful?BRCA1?mutation and?45-69%?of women who inherit a harmful?BRCA2?mutation will develop breast cancer by 70-80 years of age.

39%-49%?of women who inherit a harmful BRCA1 mutation and?11-17%?of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by 70-80 years of age.

Harmful variants in the?BRCA1?gene are also linked to a risk of fallopian tube (tubes that connect the ovaries to the uterus) cancer, primary peritoneal cancer that occurs in the lining of the abdomen, pancreatic cancer, and?prostate cancer. However, the risk of developing these types of cancer is lower than that of breast cancer.

Mutations in the?BRCA?genes increase the risk of breast cancer in males too.?Men with a BRCA2 gene mutation have a 7 in 100 chance of developing breast cancer, while men with a BRCA1 gene mutation have a 1 in 100 chance of developing breast cancer.

BRCA?Mutations and Ethnicity

The likelihood of carrying an inherited mutation in BRCA1 or BRCA2 varies across different ethnicities. In the general population, BRCA mutation(s) can be seen in about 1 in 400 people. This number increases to 2 in 100 in people of?Ashkenazi Jewish descent. The mutations found in this population are usually one of three FDA-approved variants.

Different population groups also carry different variants - for example, African Americans carry a particular variant in the BRCA1 gene that is not found in the other ethnic groups in the U.S.

Reducing Your Risk For Breast Cancer

• If you have a family history of breast, ovarian, and prostate cancer, doing a mutation analysis for your BRCA genes is recommended.
• Your healthcare provider and a genetic counselor can help you with risk assessment and understanding the implications of the test.
• Moderate to vigorous physical activity is linked with lower breast cancer risk, so it’s important to get regular physical activity.
• Alcohol consumption, even in minimal quantities, has been associated with increased breast cancer risk. So if you already have a genetic risk, it is recommended to avoid alcohol completely.

Summary

1. The?BRCA?genes produce tumor suppressor proteins that control and suppress the growth and division of tumor cells and repair DNA damage.
2. Certain harmful changes in these genes can increase the risk of developing cancer.
3. The breast cells turn cancerous when both the copies of the?BRCA1?or?BRCA2?gene are mutated.
4. Inherited mutations in the?BRCA?genes are linked to an increased risk of breast, ovarian, prostate, fallopian tube, and primary peritoneal cancer.
5. Genetic tests are mainly helpful for people with a family history of these cancers or a BRCA mutation.
6. Some ways to reduce your breast cancer risk are scheduling regular screenings, maintaining a healthy weight, and avoiding alcohol consumption.

References

• https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524247/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720154/
• https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/genes_hboc.htm
• https://www.cancer.net/cancer-types/breast-cancer-men/risk-factors
• https://pubmed.ncbi.nlm.nih.gov/32259785/

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