ToPCaP

TMPRSS2:ERG

TMPRSS2:ERG

Several members of our ToPCaP team are involved in research related to the common gene fusion in prostate cancer, TMPRSS2:ERG, the hormonally regulated somatic event that is present in the tumors of 50 percent of prostate cancer patients. These studies cover the spectrum of etiology, prognosis and precision patho-epidemiology.

Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG

In this project, we want to investigate whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes. If it does, our findings may help advance the understanding of the molecular factors linking obesity and prostate cancer outcome, and could potentially inform prostate cancer therapy development and secondary prevention strategies.

Androgen receptor CAG repeat polymorphisms and TMPRSS2:ERG prostate cancer

Experimental data suggests that heightened androgen receptor (AR) activity facilitates formation of TMPRSS2:ERG, a gene fusion present in about half the tumors of prostate cancer patients. Shorter length of a polymorphic CAG repeat sequence in the AR has been found to be associated with higher transcriptional activity. In this project, we want to investigate the association between germline genetic variation in AR, including CAG repeat length, and prostate cancer risk by TMPRSS2:ERG status. This study holds promise to identify a mechanism leading to the development of TMPRSS2:ERG positive prostate cancer.

SPINK 1 Protein Expression and Prostate Cancer Progression

SPINK1 (a serine protease) over-expression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study is to characterize the association between SPINK1 over-expression and prostate cancer specific survival in the Physicians’ Health Study and Health Professionals Follow–Up Study.

Circulating antioxidant levels and risk of prostate cancer defined by TMPRSS2:ERG

The underlying precipitating events for the TMPRSS2:ERG gene fusion formation may include DNA damage secondary to oxidative damage.Antioxidants are vital in reducing oxidative stress and concomitant DNA damage, and several epidemiological studies have investigated associations between circulating levels of antioxidants and total prostate cancer risk with mixed findings. In this project, we aim to investigate if higher levels of circulating pre-diagnostic antioxidants is associated with lower risk of developing TMPRSS2:ERG positive prostate cancer specifically.

Circulating hormone levels and risk of TMPRSS2:ERG positive prostate cancer

Experimental data suggest that heightened androgen receptor (AR) activity facilitates formation of TMPRSS2:ERG, a gene fusion present in about half the tumors of prostate cancer patients. Higher sex hormone levels have been implicated in the development of prostate cancer. In this study, we will investigate if higher levels of pre-diagnostic circulating sex hormones, such as Testosterone, is associated with higher risk of developing TMPRSS2:ERG positive prostate cancer specifically.