Genetic studies provide the most comprehensive map of breast cancer risk to date

major international study on breast cancer genetics has identified more than 350 DNA "errors" that increase an individual's risk of developing the disease. The scientists involved in the study say the errors could affect as many as 190 genes.
The results, published today in the journal Nature Genetics, provide the most comprehensive map of breast cancer risk variation to date. Researchers from more than 450 departments and agencies around the world say the findings will help provide the most detailed picture of how differences in our DNA make some women at higher risk of developing the disease than others.
Although most DNA is the same between individuals, there are also differences, called genetic mutations, that can have far-reaching effects and increase an individual's susceptibleness to disease.
Our DNA --- of the human body, containing between 20,000 and 25,000 genes. Many of these encode proteins that make up parts of the human body. Genetic mutations can be in genes that alter proteins. However, most genetic variants are outside the gene and sometimes regulate the function of the gene, increasing or decreasing or even shutting down its "volume". Finding the genes targeted by these variants is not easy.
Most diseases are complex multigene diseases - in other words, there is no single genetic mutation or gene that causes the disease, but a combination of many diseases works together to increase an individual's likelihood of developing a particular disease. Breast cancer is such a disease.
Previous genome-wide association studies (GWAS) involved comparing a patient's DNA with healthy controlled DNA and found about 150 genomic regions that significantly affect breast cancer risk. In these areas, researchers know that one or more genetic changes can affect the risk of cancer, but they are rarely able to identify specific mutations or genes involved. Fine mapping studies such as these allow scientists to narrow down the variants that cause the disease, how they work, and predict which genes are involved.
Dr Laura Fachar, of the Wellcome Sanger Institute, said: "We have learned from previous studies that mutations in our DNA increase the risk of breast cancer, but scientists are rarely able to determine exactly which genes are involved. We need this information because it gives us better clues as to what causes the disease, so how we can treat or even prevent it. In
, researchers from hundreds of institutions around the world teamed up to compare the DNA of 110,000 breast cancer patients with that of about 90,000 healthy controls. By studying it more carefully than before, they identified 352 risk variables. It's not clear how many genes these genes target, but researchers have identified 191 genes with reasonable confidence. Less than one in five people used to be recognized.
Dr Alison Dunning, of the University of Cambridge, said: "The staggering number of newly discovered breast cancer genes gives us more genes to study, most of which have not yet been studied. This will help us understand in more detail how breast cancer occurs and develops. However, the current number of genes known to work highlights the complexity of the disease.
of the newly discovered genetic variants, one-third of women tend to develop hormone-reactive breast cancer, the type of disease found in four-fifths of breast cancer patients who respond to hormone therapy such as tanthoxifen. A 15% genetic mutation makes women more likely to develop rare estrogen receptor-negative breast cancer. The remaining genetic variants play a role in both types of breast cancer.
In most cases, genetic changes affect gene expression - in other words, how active a particular gene is and how many specific proteins it creates - rather than changing the type of protein itself. For example, nine different variants regulate the same gene, the estrogen-like (ESR1) gene. Many other variants affect where estrogen-like proteins bind in DNA, which in turn regulates other genes. This highlights the importance of the ESR1 gene and its protein product, estrogen, in breast cancer development.
The researchers say that while each genetic mutation only increases the risk of breast cancer very small, together, these mutations will allow them to "fine-tune" genetic testing and give women a clearer understanding of their genetic risks. This will then allow doctors and clinicians to advise on the best strategies to reduce risk and prevent the onset of disease.
Professor Doug Easton, also from Cambridge University, said: "Our work would not have been possible without the help of 200,000 volunteers allowing us to study their DNA. It is also evidence of the assistance of hundreds of researchers from around the world working on the study. ”（cyy123.com）