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Israeli Scientists Develop New computational genetic model to predict Breast Cancer

Breast Cancer

Israeli Researchers from Tel Aviv University may have found a new way to predict the onset of breast cancer through genetic testing. They say that they have developed a computational model that makes it possible to predict each woman’s genetic risk of developing breast cancer based on her genetic profile. The new computational model, they say, will allow, for the first time in Israel, the determination of a personal genetic risk score for breast cancer based on the genetic profile of each woman. This development could form the basis for the implementation of a personalized early detection policy – women at high risk of breast cancer will be advised to start screening tests for early detection from a younger age, and more frequently.

The research was based on a large-scale international study that included genomic data of about a quarter of a million women with and without breast cancer and applied its findings to about 2000 Israeli women.

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The use of genetics – DNA – in all manner of medical and scientific research has moved forward by leaps and bounds over the years. First, there was the advent of genetic testing that could be used in criminal investigations. Remember the O.J. Simpson trial back in 1995? They found his DNA all over the crime scene. OK, bad example. But DNA has been used for decades now to both convict as well as exonerate suspects in numerous crimes around the world.

And DNA testing has also been used for years to determine if someone may be a carrier for a disease of some sort. If the gene is recessive, the carrier will not suffer from it. But if they marry another carrier of the same gene then there will be a 50/50 chance that their children will suffer from the disease.

And numerous diseases are genetic, passed from parent to child. Some have no treatment. But if a family member suffered from such a disease and genetic testing can tell a person if they will someday suffer from it too, then at least they will be able to prepare for the inevitable.

But for many illnesses, such as cancer, early detection is the key to getting the proper treatment. In far too many cases people have been forced to deal with the reality that if only the cancer had been detected sooner they might have at least been able to live for many more years. For example, the famed host of “Jeopardy” Alex Trebek died from pancreatic cancer. This is a form of cancer that cannot – at least as of now – be detected before it is too late. Once pancreatic cancer is uncovered in the body the damage it caused is already too extensive to save the person’s life.

Now, imagine if any such disease can be predicted through genetic testing. Even if there is not a 100% – or even more than 50% – likelihood that the person will get sick if they have the related gene, they would at least know it would be worthwhile to get tested regularly for any signs of the disease.

And there is also the issue of cost. Insurance companies will not approve the expense of preemptive testing without any evidence of the presence of a disease. But if people can get genetic screening early in life then there would be justification for constant screenings for a particular illness.

As for the new process developed by TAU scientists, the team of researchers explains that “Our method will allow the health system to move to a personalized early detection policy – when those who are identified as being at high risk will be tested from a younger age and more frequently. Focusing the screening tests using the model may save lives and will save health system resources.”

The research was conducted by doctoral student Hagai Levi under the guidance of Prof. Rani Elkon from the Department of Human Molecular Genetics and Biochemistry at the Tel Aviv University School of Medicine, and Prof. Ron Shamir from the Blavatnik School of Computer Science at Tel Aviv University. The research was carried out in collaboration with Prof. Shai Carmi from the Faculty of Medicine at Hebrew University, with Prof. Shay Ben Shachar – Director of Precision Medicine and Genomics at Clalit Research Institute, and with Dr. Naama Elefant from the Hadassah University Medical Center. The study was published in the Journal of Medical Genetics.

Prof. Elkon explains that in 2003 the sequencing of a draft of the human genome was completed, creating new opportunities for improvement in medicine, with an emphasis on personalized medicine. The basic idea was that the better we know how to determine whether a certain person is genetically predisposed to a certain disease, the more we can take appropriate preventive measures.

The studies assign a ‘genetic risk score’ to each participant, and in large samples, these scores typically follow a bell distribution: the majority of the population are in the middle, and at the two extremes are people with extremely high or low risk scores of having the same disease. The challenge of medicine is to identify in advance those people who have a high genetic tendency to get sick, especially of diseases that can be prevented or detected in early stages.

The current study was based on the findings of a huge international GWAS study that identified genetic variants associated with breast cancer by analyzing the genetic profiles of approximately 130,000 breast cancer patients from dozens of medical centers in Europe and the United States alongside approximately 100,000 healthy women who served as a control group.

The researchers built a computational genetic model to predict the risk to the Israeli participants by determining a ‘genetic risk score’ for each woman and dividing the participants into deciles according to the risk score they received. The findings revealed that women in the top decile of the score calculated by the model have a four times higher chance of getting breast cancer compared to women in the bottom decile. In other words: the genetic risk score has a significant ability to predict the risk of breast cancer among the population examined. The researchers confirmed their findings on another sample of breast cancer patients collected by physician-researchers in the oncology and genetics departments at the Hadassah Medical Center.



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