Plasma-Free Insulin Growth Factor 1 as a Predictor of Lethal and Advanced Prostate Cancer in Physicians Health Study and Health Professionals Follow-Up Study
Abstract
Results from this project will prevent many men from receiving unnecessary prostate cancer treatment while also retaining the mortality benefits of prostate-specific antigen (PSA) screening. Prostate cancer is the second-leading cause of cancer death in U.S. men, but most men diagnosed with prostate cancer will die of other causes. Many men with benign disease still receive aggressive treatment and often suffer significant quality of life consequences, such as urinary incontinence, impotence, and sexual dysfunction. This is largely because PSA screening, the most effective and common prostate cancer screening tool, detects both lethal and indolent disease and cannot adequately discriminate between the two. However, PSA screening helps identify prostate cancer at earlier stages and has saved thousands of lives over the last two decades. Thus, PSA screening should not be abandoned, but needs improvement. Our main goal is to determine whether free IGF-1 levels can be used to improve clinicians’ ability to identify men who will (and will not) develop lethal prostate cancer. Free insulin-like growth factor (IGF-1) is a biomarker in the blood. We previously found that total IGF-1 is one of the strongest established predictors of advanced prostate cancer, but the prediction level is not strong enough for clinicians to make treatment, biopsy, and screening decisions based on total IGF-1 levels. However, about 95% of total IGF-1 on average is not bioavailable and not biologically active. We also previously showed that levels of acid-labile subunit (ALS), another related blood biomarker that binds free IGF-1 and renders it inactive, is also related to risk of advanced prostate cancer. The small portion total IGF-1 that is free (bioavailable) is biologically active and likely is much more strongly predictive of prostate cancer progression. We have found that free IGF-1 and total IGF-1 do not strongly track with each other. Thus, free IGF-1 levels provide independent information, likely at magnitudes large enough to use clinically. Until now, there has not been a way to accurately measure free IGF-1, so it has been impossible to properly study the relationship between free IGF-1 and prostate cancer progression. Our co-investigator Dr. Michael Pollak has developed and validated an assay that accurately measures free IGF-1. If our hypothesis holds, free IGF-1 assays can be readily implemented in clinical settings, leading to rapid reductions in overdiagnosis and subsequent unnecessary treatment. We will also measure free and total IGF-1, PSA, and ALS in 1,072 prostate cancer patients (536 with lethal disease and 536 with non-lethal disease). All measurements will be based on stored blood drawn before prostate cancer diagnosis, which is important since we want to determine free IGF-1’s ability to predict future progression. By comparing free IGF-1 levels across these two groups, we can determine whether free IGF-1 levels can help distinctively predict lethal (versus non-lethal) prostate cancer. We will also determine whether considering free IGf-1 and ALS levels, in addition to PSA, will improve our predictive ability to identify potentially lethal prostate cancer, as distinguished from indolent prostate cancer that does not require treatment. We have an ideal research setting to tackle this research question, because we already have the stored blood samples from before the prostate cancer diagnosis and a wealth of other data on these men. These data include blood levels of many biomarkers and hundreds of metabolites. We also have detailed biochemical data from the tumors of many of these men. Taken together, these data will enable us to further explore the biological mechanisms for IGF1 functioning, perhaps leading to new avenues for treatment. This project will lead to rapid and significant benefits for future prostate cancer patients, as it will enhance early diagnosis and spare many men from unnecessary tre
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810158
Entities
People
- Meir J. Stampfer
Organizations
- United States Army