Identification Of Prostate Cancer Susceptibility Loci

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Genetics
Article Date: 20 Apr 2008 - 0:00 PDT

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UroToday.com - Dr. Kiermeney (Nijmegen) presented data on susceptibility loci in prostate cancer (CaP). Searching for genes in this setting can be done by looking for functional variants of genes suspected to be involved. Linkage studies in high-risk families look for co-segregation of markers and search for closely located genes. Three rare genes have been identified after a worldwide study. A combined approach was more recently applied. It is a hybrid of candidate genes and family linkage. The researchers look for ancestral mutations transmitted to the next generation along with a stretch of the chromosome. The segments get smaller with successive generations. The allele is compared to controls for frequency. Meiotic recombinations are not random and correlation between markers can be assessed by using select single nucleotide polymorphisms. tagSNPs are selected SNPs and they are correlated with other SNPs in certain areas referred to as blocks. Combinations of SNPs can assessed and over 900,000 combinations were assessed. The yield has been relatively small. However, stringency can be increased by applying the statistical fining to subsequently larger populations.

Four genome wide association studies in CaP have been performed. Most of these studies looked at over 1,500 cases of CaP and matched controls. Region 8q24 was a region identified as correlating with the development of CaP. It was found in both the US study and the Icelandic study. This chromosome region is replicated in numerous areas across populations and is also associated with increased risk for the development of colon cancer. 17q12 (linked to type II diabetes) and 17q24 are regions also found as associated with the risk of developing CaP. Recently, a region on chromosome 10 has been identified and is under investigation. He concluded that larger samples, better assays, and better phenotyping in the future and studying all the variants and identifying the functional mechanisms will provide new knowledge for testing, therapy and personalized medicine.

Presented by: L. Kiermeney, MD, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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