BRCA only explains a fraction of breast cancer cases; genes related to metabolism may also increase risk

A new study has identified 80 genes that may increase the risk of developing diabetes breast cancer – 70 of these were previously unknown to be related to the disease.

This gene variants – genes with a clear difference in their DNA code – were discovered by scientists who analyzed the genomes of people from a dozen families. All twelve families have a high incidence of breast cancer, but their cancers had no known genetic causes.

Most cases of breast cancer happen spontaneously, meaning they do not arise from genetics passed down through families. However, about 5% to 10% of cases are hereditarywhich occurs in people with a family history of the disease. of those individuals about 30% will carry mutations in two genes known as BRCA1 and BRCA2, which is normally the case help repair damaged DNA in cells but defective in cancer. Other people may carry different gene variants that increase their risk, such as PTEN And TP53.

However, many families do not have an answer to the genetic cause of their disease.

One possible reason for this is that large-scale genetic studies of cancer have mainly focused on women of European descent Dr. Gal Passilead author of the new study and a PhD candidate in computer science at the Hebrew University of Jerusalem. These likely overlooked gene variants that might be carried by ethnic groups not included in the analyses, he told LiveScience.

To help bridge this gap, Passi and colleagues analyzed the genomes of twelve families with Jewish ancestors from the Middle East, North Africa and Ashkenazia. This included 35 people with breast cancer and 5 without the disease. Breast cancer was common in these families, yet every family member tested negative for known genetic risk variants for the disease.

Within the genomes of these people, the researchers identified 1,218 mutations that were shared among the individuals who had breast cancer. Then they used a combination of machine learning techniques – sort of artificial intelligence – and an analysis to predict which types of proteins each of the genes carried instructions for. In this way they predicted which of the gene variants are likely to produce proteins that are carcinogenic.

They came up with 80 variants that are significantly associated with an increased risk of developing breast cancer.

Eight of those gene variants – carried by members of seven of the families – coded for proteins involved in fatty acid metabolism. Fatty acids are the building blocks of fat molecules, which occur in the body’s cells break down to release energy. Although it’s just a theory at this stage, it’s possible that breast cancer cells somehow target these fatty acid breakdown pathways to improve their chances of survival, Passi said. This would make sense, because tumors are very energy demanding tissues.

In a separate experiment, the researchers analyzed the genomes of about 10,000 breast cancer patients, whose information was stored in a large genetic database. They found that the eight gene variants identified in their study were carried by 9%, or about 900, of these individuals.

They also found that three of these variants were associated with low survival rates in the patients who carried them, compared to people who carried different versions of the genes.

Taken together, these data support the idea that these 80 gene variants are relevant to breast cancer.

The researchers now want to do lab experiments to see if the gene variants really produce proteins that change how tumors form and grow, Passi said. In their current study they only made predictions about the behavior of the tumors, so now these need to be confirmed. The team would also like to see if they can identify more cancer-related variants in a larger number of families with the disease.

Identifying variants like these is important because it could pave the way for more inclusive genetic testing for breast cancer and, hopefully, the development of treatments that target each unique type of cancer, Passi said. One of the gene variants that emerged in the study, called HSD17B4, has already been proposed as a gene variant potential drug target in breast cancer, he added.

Do you ever wonder why? some people build muscle more easily than others or why freckles appear in the sun? Send us your questions about how the human body works [email protected] with the subject ‘Health Desk Q’, and you may see your question answered on the website!