Genetic Variations in Mitochondria and Prostate Cancer Aggressiveness and Progression in Caucasian and African American Men
Annual rept. 1 Jul 2012-30 Jun 2013
M D ANDERSON CANCER CENTER HOUSTON TX
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It has been suggested that some inherited mtDNA variants could have an adverse effect by increasing the generation of reactive oxygen species ROS. Besides the sequence variations in mtDNA, the mtDNA CNV might also affect cancer risk by disturbing crosstalk between the mitochondria and the nucleus, and consequently altering nuclear DNA stability. Variability in the mtDNA sequence and copy number might be extremely relevant to prostate cancer because oxidative stress has been suggested to play a significant role in prostate cancer carcinogenesis. Even more intriguingly, the geographic and racial polymorphisms of mtDNA might have implications in the racial disparity of prostate cancer because African Americans are at a disproportionately higher risk for many oxidative stress related medical conditions, including prostate cancer. In this current proposal, we plan to utilize the valuable biospecimens and data collected through North Carolina-Louisiana Prostate Cancer Project PCaP to comprehensively study the associations between mtDNA polymorphismshaplogroups and prostate cancer tumor characteristics at baseline and progression in both CA and AA men. Our hypothesis is that genetic variations sequence and copy number in mtDNA are associated with prostate cancer aggressiveness at diagnosis and prostate cancer progression. So far, we have completed genotyping analyses for 75 genetic polymorphisms in all study subjects for Aim 1. In Aim 2, we have completed CNV analyses in about 500 study subjects. We have not started Aim 3 yet.
- Anatomy and Physiology
- Medicine and Medical Research