In kidney cancer world, there’s a lot of biomarkers right now, but we still face a big barrier to predicting response to kidney cancer survival or response. And in kidney cancer genetics, we know for a fact that previously, for the past 15 years, we’ve seen that kidney cancer heritability is approximately 38%, which means that the incidence of kidney cancer and having kidney cancer is associated with single nucleotide variants and human genetic germline DNA...
In kidney cancer world, there’s a lot of biomarkers right now, but we still face a big barrier to predicting response to kidney cancer survival or response. And in kidney cancer genetics, we know for a fact that previously, for the past 15 years, we’ve seen that kidney cancer heritability is approximately 38%, which means that the incidence of kidney cancer and having kidney cancer is associated with single nucleotide variants and human genetic germline DNA. And we were interested to see if the polygenic risk score, which means summing all the single nucleotide variants and compiling them into one score, is associated with survival. And what we did in our study is that we compiled a cohort of 495 patients diagnosed with kidney cancer at Dana-Farber that had tumor sequencing done, and then we imputed their germline genetics using a pipeline called STITCH. And this pipeline was developed by my mentor, Dr. Alexander Gusev, which basically leverages the targeted sequencing of Oncopanel to impute germline genetics. And what we found that was interesting is that among more than 300 polygenic risk scores that we computed, two were significantly associated with survival and met the false discovery rate and specifically polygenic risk of platelets that had a 37 percent – the higher the score the patient has, the higher the risk of death by 37 percent and what was interesting is that when we adjusted for the platelet levels in these patients, we saw that this signal disappeared, which tells us that this specific polygenic risk curve of platelets is mediated through the platelet effect and not any other pathway. Another thing that we found in our study is when we looked at all cancer types and stratified by cancer types, we saw that this specific signal was exclusively only seen in the kidney cancer cohort. So if we take from the initiation of therapy in each patient from different cancer types and we look at the polygenic risk of platelets in these patients, we see that this signal is only seen in the kidney cancer. And what this tells us, what could this possibly tell us is that the thrombocytosis that we see in patients and we know from the literature that is associated with worse prognosis, worse survival, and higher risk of recurrence is not only due to treatment effect or cancer diagnosis per se, but it’s also inherently due to germline DNA that the patient might have.
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