Steven Lehrer1, Peter H Rheinstein2. 1. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A. steven.lehrer@mssm.edu. 2. Severn Health Solutions, Severna Park, MD, U.S.A.
Abstract
BACKGROUND: Androgen deprivation therapy (ADT) is extensively employed in treatment of prostate cancer. Some studies have found increased risk of Alzheimer's disease and cognitive impairment in patients treated with ADT. AIM: Since the uncertainty about ADT and dementia might relate to the genetics of prostate cancer and Alzheimer's disease, we used the Cancer Genome Atlas (TCGA) to examine the relationship between genes implicated in Alzheimer's disease and genes implicated in prostate cancer in men with prostate cancer. MATERIALS AND METHODS: The genomics of 492 prostate cancer cases in the Genomic Data Commons TCGA Prostate Cancer data set were examined. RESULTS: Alterations (mutation, amplification or deletion) in prostate cancer gene speckle-type POZ protein (SPOP) significantly co-occurred with alterations in Alzheimer's disease gene bridging integrator-1 (BIN1). Alterations in prostate cancer gene spectrin alpha 1 (SPTA1) significantly co-occurred with alterations in Alzheimer's disease gene CD2-associated protein (CD2AP) (p<0.001). The presence of somatic mutations (deleterious and missense/in frame) in SPOP disturbs BIN1 gene expression. SPOP and BIN1 RNA expression in 492 prostate cancer specimens was significantly positively correlated (p<0.001). Increased expression of SPOP in 492 cases of prostate cancer was associated with reduced survival (p=0.00275). BIN1 forms part of a network that interacts with the MYC oncogene, which is activated at the earliest phases of prostate cancer and is linked to disease aggressiveness. Men receiving ADT had tumor with a significantly higher Gleason score (p=0.023). Gleason score and BIN1 RNA expression in 499 prostate cancer specimens were significantly correlated (p<0.001). CONCLUSION: The severity of prostate cancer is determined by the genetics of the tumor itself, possibly at least in part by the interactions of SPOP/BIN1, MYC/BIN1 and SPTA1/CD2AP. Oncologists treats higher grade prostate cancer with more ADT, which serves as a surrogate marker for disease severity. A weakness of our study is that we did not examine Alzheimer's disease or dementia at all in patients with cancer, only co-occurrence of genetic alterations. Nevertheless, our analysis of TCGA data does not support the idea that ADT causes Alzheimer's disease or dementia. Copyright
BACKGROUND:Androgen deprivation therapy (ADT) is extensively employed in treatment of prostate cancer. Some studies have found increased risk of Alzheimer's disease and cognitive impairment in patients treated with ADT. AIM: Since the uncertainty about ADT and dementia might relate to the genetics of prostate cancer and Alzheimer's disease, we used the Cancer Genome Atlas (TCGA) to examine the relationship between genes implicated in Alzheimer's disease and genes implicated in prostate cancer in men with prostate cancer. MATERIALS AND METHODS: The genomics of 492 prostate cancer cases in the Genomic Data Commons TCGA Prostate Cancer data set were examined. RESULTS: Alterations (mutation, amplification or deletion) in prostate cancer gene speckle-type POZ protein (SPOP) significantly co-occurred with alterations in Alzheimer's disease gene bridging integrator-1 (BIN1). Alterations in prostate cancer gene spectrin alpha 1 (SPTA1) significantly co-occurred with alterations in Alzheimer's disease gene CD2-associated protein (CD2AP) (p<0.001). The presence of somatic mutations (deleterious and missense/in frame) in SPOP disturbs BIN1 gene expression. SPOP and BIN1 RNA expression in 492 prostate cancer specimens was significantly positively correlated (p<0.001). Increased expression of SPOP in 492 cases of prostate cancer was associated with reduced survival (p=0.00275). BIN1 forms part of a network that interacts with the MYC oncogene, which is activated at the earliest phases of prostate cancer and is linked to disease aggressiveness. Men receiving ADT had tumor with a significantly higher Gleason score (p=0.023). Gleason score and BIN1 RNA expression in 499 prostate cancer specimens were significantly correlated (p<0.001). CONCLUSION: The severity of prostate cancer is determined by the genetics of the tumor itself, possibly at least in part by the interactions of SPOP/BIN1, MYC/BIN1 and SPTA1/CD2AP. Oncologists treats higher grade prostate cancer with more ADT, which serves as a surrogate marker for disease severity. A weakness of our study is that we did not examine Alzheimer's disease or dementia at all in patients with cancer, only co-occurrence of genetic alterations. Nevertheless, our analysis of TCGA data does not support the idea that ADT causes Alzheimer's disease or dementia. Copyright
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