About 5% to 10% of breast cancers are thought to be hereditary, caused by abnormal genes passed from parent to child.
Genes are short segments of DNA (deoxyribonucleic acid) found in chromosomes. DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body.
Think of your genes as an instruction manual for cell growth and function. Abnormalities in the DNA are like typographical errors. They may provide the wrong set of instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain the same gene. This is like having an instruction manual in which all the copies have the same typographical error.
We’ve known for many years that mutations in the BRCA1 and BRCA2 genes are linked to a higher risk of breast cancer. Women who have a BRCA1 or BRCA2 mutation (or both) can have up to a 72% risk of being diagnosed with breast cancer during their lifetimes. Now, we also know that other gene mutations are linked to breast cancer, including mutations in the PALB2, TP53, PTEN, and the BRIP1 genes.
A research team at the Institute of Cancer Research in London, UK, has associated 110 genes with a higher risk of breast cancer.
The research was published online on March 12, 2018 by the journal Nature Communications. Read “Capture Hi-C identifies putative target genes at 33 breast cancer risk loci.”
To do the study, the researchers used a new high-throughput genetic analysis technique, called Capture Hi-C, to look at 63 areas of the human genome previously associated with breast cancer risk through mapping analysis. Capture Hi-C is a high-resolution technique that can study interactions between different regions of the genome, something that hasn’t been possible before.
A genome is a living thing’s complete set of DNA, including all of its genes. Small sections of DNA can interact with completely different parts of the genome they’re not close to through a phenomenon known as DNA looping. So a gene linked to breast cancer could be activated by another gene it usually wouldn’t have contact with. DNA looping can make identifying specific genes linked to high risk of disease less straightforward because it’s difficult to anticipate which specific genes will interact during DNA looping. Capture Hi-C overcomes this issue.
"Our study took the high-level maps of breast cancer risk regions and used them to pull out specific genes that seem to be associated with the disease," said Olivia Fletcher, team leader in functional genetic epidemiology at the Institute of Cancer Research, and co-corresponding author of the study. "We studied how DNA forms loops to allow physical interactions between a DNA sequence in one part of the genome and a risk gene in another. Identifying these new genes will help us to understand in much greater detail the genetics of breast cancer risk. Ultimately, our study could pave the way for new genetic tests to predict a woman's risk, or new types of targeted treatment."
The study found that some of the 63 regions of the genome were physically interacting with genes more than a million letters of DNA code away.
The researchers identified 110 genes associated with breast cancer in 33 of the regions they studied. In the other 30 regions, they were unable to identify specific genes linked to breast cancer. Most of the genes this study associated with breast cancer had not been linked to breast cancer risk before. Much more research is needed to figure out the role these genes play in the disease, as well as whether the genes and any mutations in them can be identified using multigene panel testing.
"Large-scale genomic studies have been instrumental in associating areas of our DNA with an increased risk of breast cancer," said Paul Workman, chief executive of the Institute of Cancer Research. "This study brings these regions of DNA into sharper focus, uncovering a treasure trove of genes that can now be investigated in more detail. The ways in which particular genes influence cancer risk are highly complex. In the future, a better understanding of the genes identified in this study could lead to the discovery of new targeted drugs, or new strategies to improve diagnosis or prevention of the disease."
If you have a strong family history of breast cancer, you may want to talk to your doctor or a licensed certified genetic counselor about your family history and ask if having a multigene panel test makes sense for you. You also may be considering ordering an at-home genetic test, such as Color or 23andMe. No matter which genetic test you have, it is important to know exactly which genes and mutations the test is analyzing. A licensed certified genetic counselor or your doctor can help you understand the test and accurately interpret the results.
For more information on genetic testing, including types of genetic tests and how results are reported, visit the Breastcancer.org Genetic Testing pages.
For more information on genes and genetic mutations linked to breast cancer, as well as all the risk-lowering steps you can take if you have a genetic mutation, visit the Breast Cancer Risk Factors: Genetics page in the Breastcancer.org Lower Your Risk section.
Editor’s Note: This article was updated on Dec. 20, 2018, with updated information on cancer risks associated with BRCA mutations.