A genetic-based approach to personalized prostate cancer screening and treatment

Abstract

Purpose Recent advances in sequencing technologies has allowed for the identification of genetic variants within germline DNA that can explain a significant portion of the genetic underpinnings of prostate cancer. Despite evidence suggesting that these genetic variants can be used for improved risk stratification, they have not yet been routinely incorporated into routine clinical practice. This review highlights their potential utility in prostate cancer screening. Recent Findings There are now almost 100 genetic variants, called single nucleotide polymorphisms (SNPs) that have been recently found to be associated with the risk of developing prostate cancer. In addition, some of these prostate cancer risk SNPs also have been found to influence PSA expression levels and potentially aggressive disease. Summary Incorporation of panels of prostate cancer risk SNPs into clinical practice offers potential to provide improvements in 1) patient selection for prostate cancer screening 2) PSA interpretation (e.g. by correcting for the presence of SNPs that influence PSA expression levels, 3) decision for biopsy (using PC-risk SNPs) and possibly the 4) decision for treatment. A proposed clinical algorithm incorporating these PC-risk SNPs is discussed.

What's new in screening in 2015?

“…Despite evidence suggesting that these genetic variants can be used for improved risk stratification, they have not yet been routinely incorporated into routine clinical practice. Next to several original publications[58, 59], Helfand et al 60] reviewed their potential utility in PC screening and claim that it is possible that SNPs analyses can help risk stratify men who have increased susceptibility and target PSA based screening only to those men who are at increased risk. Same holds for SNPs that are strongly associated with PSA levels (so-called PSA-SNPs).…”

A Review of Prostate Cancer Screening Guidelines for African American Veterans

“…Certain molecular markers have also been linked to the clinical course and disease outcomes in men with prostate cancer [26,27]. For instance, several studies have identified multiple single nucleotide polymorphisms (SNPs) that are preferentially expressed in African-Americans [27]. Approximately 100 genes containing SNPs have been linked to an increased susceptibility to prostate cancer [27].…”

“…For instance, several studies have identified multiple single nucleotide polymorphisms (SNPs) that are preferentially expressed in African-Americans [27]. Approximately 100 genes containing SNPs have been linked to an increased susceptibility to prostate cancer [27]. Single nucleotide polymorphisms are especially valuable in disease detection, monitoring, and screening because they are stable throughout the lifetime of the individual and are not affected by external factors, such as lifestyle [27].…”

Glycogen synthase kinase-3: A potential preventive target for prostate cancer management

“…Despite extensive efforts in developing novel biomarkers in this regard, no single biomarker can accurately predict the aggressiveness of this cancer thus far [15]; largely due to the heterogeneous properties of prostate cancers between individual patients and/or even among different loci within a given tumor mass [3]. By recognizing the distinct genetic differences between patients [16], personalized medicine is emerging as a new strategy for prostate cancer management. Still, adequate biomarkers are needed to determine tumor aggressiveness.…”