BERKELEY, CA (UroToday.com) - All of the information required to build and maintain a human body is encrypted within its genome that consists of more than 3 billion DNA base pairs. Every generation, this genetic information has to be passed on with little or no alterations to allow the survival of the human species. As a result, the genomes of different individuals are nearly identical, with the number of genetic variations being limited to approximately 1 % of the DNA. However, these little variations explain the many inter-human phenotypic differences. Indeed, an individual’s genotype leads to the development of its phenotype, which is the individual’s observed properties, such as morphology, behavior, but also susceptibility to disease.
One of the most evident forms of genetic variation is the existence of single nucleotide polymorphisms (SNPs), which are DNA sequence variations occurring commonly within a population (≥ 1%) in which a single nucleotide (A, T, C or G) in the genome differs between individuals. The minor frequency allele (the allele with the lowest frequency in a population) may change gene expression and/or protein structure when compared to the major frequency allele.
Epidemiological studies have clearly shown that prostate cancer (PCa) is one of the most inheritable cancers with race and family history being primary risk factors to develop this disease. Although highly inheritable, the clinical heterogeneity of this disease clearly reflects a non-Mendelian, multifactorial inheritance pattern. It is because of the limitations of current clinical and pathological disease staging that there has been an increasing interest into the development of (genetic) biomarkers assisting clinicians in their everyday decision making. It has hence become a major field of interest to determine the role of SNPs in the clinical field. While each individual SNP might only have a limited impact on disease susceptibility, the accumulation of risk SNPs might lead to a higher risk of developing the disease, therapy resistance, etc.
Since 2008, numerous genome-wide association studies (GWAS) have been conducted, comparing the prevalence of SNPs between patients with PCa and healthy controls. This resulted in the description of more than 77 loci that are associated with PCa. With this knowledge, many researchers focused their research on finding SNPs which are correlated with more specific questions on disease development, therapeutic response, and others.
The question currently still remains whether SNPs can help the clinician in improving the everyday management of PCa patients. We have reviewed the literature highlighting some of the issues that arise when applying the current knowledge on genetic variation to diagnostic or therapeutic use in clinical practice.
Written by:
Thomas Van den Broeck, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Laboratory of Molecular Endocrinology
Dept. Celullar and Molecular Medicine, KU Leuven
Dept. of Surgery - Urology, UZ Leuven
Campus Gasthuisberg O&N1
Herestraat 49
B-3000 Leuven
Belgium