Cancer risk screening. Next Generation Sequencing of your genome. 3

Cancer risk screening. Next Generation Sequencing of your genome. 3

Cancer risk screening. Next Generation Sequencing of your genome. 3

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Next Generation Sequencing, NGS. Whole Exome Sequencing, WES. It allows more granular assessment of individual cancer risks. I predicts reactions to many medications. When a child is born, soon doctors will hand a flash drive with child’s genome. It will help to assess lifetime risks to health. 1 in 4 people is found to have DNA mutations that affect diagnostic and treatment considerations.


Cancer risk evaluation by next-generation sequencing, NGS. Early cancer risk detection by Whole Exome Sequencing, WES. It is becoming more popular and more available. Next-generation sequencing is certainly cheaper. What are the opportunities to screen for increased cancer risks by whole genome sequencing? Dr. Anton Titov, MD. I think this is a way to go. This is early cancer diagnosis strategy in the really near future. There is a project of the European Union 2020 or Horizon 2020. This is the way I envision gene sequencing for cancer risks detection. A child is going out of the delivery room. Physicians will give his parents small disk or a flash drive key with words. This is the genome of your child. Whenever you approach the physicians, be careful - they are dangerous! Consult with this DNA data. Because it's been shown that genes affect how you respond to medicines. When I give somebody with a fever paracetamol, I give 500 to 1000 milligrams for everyone. But obviously everyone has different metabolism rate. Everyone is going to react differently. With paracetamol, the gap between efficacy and toxicity is huge. Dr. Anton Titov, MD. You're not concerned about anything. But for other medication the therapeutic window is much narrower. Dr. Anton Titov, MD. Cancer risks detection is definitely worth a personal approach. This is called pharmacokinetics. Genomic data can also tell us a lot about risk of developing different cancer. The disease you're prone to and maybe where you should put your prevention efforts. Sometimes somebody has a lot of obesity-predisposing genes. Obtain medical second opinion on cancer. Then we'll be able to watch weight more carefully, or vice versa. I think whole genome sequencing is going to tell us a lot about personal health risks. Obviously it's not going to replace clinical medicine. It's going to help us a lot in education of patients. Personal genome sequencing will help to prevent diseases and overcome them. Whole exam sequencing will tell us how to educate patients. Dr. Anton Titov, MD. Personal genomics data is definitely going to be used much sooner than many think. In the next decade it's going to happen. Most healthy people in the Western Hemisphere are going to use personal genomic data. Prices of gene sequencing will go down to a few hundred dollars. This is something that everyone can afford. You published a very interesting paper that looked at 25 healthy people. It turns out that 24% of them - almost 1 in 4 have a "management changing" DNA mutations. These mutations could predispose them to increased risk of cancer and heart disease. 80% of people tested harbored 1 to 3 different mutations. These mutations required alterations in the dosages of medications that are approved by the US FDA. Could you please tell about gene sequencing to find cancer mutations in healthy people? Dr. Anton Titov, MD. I was surprised. I did not expect so much knowledge from this DNA genome sequencing. It's going to change my clinical judgment. Our early cancer detection methods will be changed not only for me, but for my entire team. And indeed, we did. Dr. Nadir Arber, MD. We found someone who is prone to develop breast cancer because she had a BRCA mutation. But clinical history did not tell us about breast cancer risk. Dr. Nadir Arber, MD. We had a daughter and her mother. Mother has a tendency to develop colon polyps. Dr. Anton Titov, MD. Whenever I did a colonoscopy, I found polyps. Dr. Anton Titov, MD. Obtain medical second opinion on cancer. Then we found a gene that predisposed her to colon polyps and colon cancer. It showed us matching between the genotype and the phenotype. The daughter did not have this gene. Dr. Nadir Arber, MD. We told a daughter this. Dr. Nadir Arber, MD. We don't have to go and do new colonoscopy every 1-2 years. Because you do not carry the gene that your mother carries. Dr. Anton Titov, MD. You can have it both ways. All this information was just from whole exome sequencing. I think the fidelity of sequencing was not that great. In the future we will improve whole genome sequencing quality. I'm sure we can gain much more information about early cancer detection. But there is a lot of things. There are a lot of cancer-causing genes that we still do not know about. Dr. Nadir Arber, MD. We don’t know their functions. Dr. Nadir Arber, MD. We still do not exactly know what is meaningful among all these genes. It is much more complicated. Dr. Nadir Arber, MD. We do the whole exome sequencing. This is only about 1% of all the DNA bases. There is a lot of DNA between the exons. I don't believe in the term "garbage DNA”. Everything has a meaning. But at the same time it's very interesting that interpretation of the genome is also very important. Of course, there is a lot of gray areas in while genome sequencing to find cancer risks. But some of the genes have well-known mutations that can predispose people to cancer. Therefore we shouldn't pursue an "ostrich strategy” for cancer risk detection. Dr. Nadir Arber, MD. We should really know what's in the genes. And a mutation that is found is a clear-cut answer for cancer risk. Obtain medical second opinion on cancer. Then it requires manual curation of genome as was done in your paper. Obtain medical second opinion on cancer. Then it requires some altered behavior with cancer risk mitigation. I absolutely agree!

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