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Apr 2, 2007

Three Seperate Studies Implicate Variations on Chromosome 8 in Prostate Cancer

  • Teams of scientists have discovered genetic variants on the same region of chromosome 8 that are associated with  prostate cancer in Icelandic and African American men as well as white men in the U.S. and of north European decent. The results of all three studies appear in the May 1, 2007, issue of Nature Genetics and were published in the online version on April 1.

    A variation in a portion of DNA strongly predicts prostate cancer risk. Additionally, this common variation may be responsible for up to 20% of prostate cancer cases in white men in the U.S., reports researchers from the NCI and the Cancer Genetic Markers of Susceptibility (CGEMS) initiative.

    This gene variation, rs6983267, was discovered on chromosome 8. The region the CGEMS study identified on chromosome 8, 8q24, is marked by a number of SNPs, including rs6983267. This segment of DNA has few known or predicted genes for prostate cancer.

    The researchers also confirmed that a previous finding of a different variant, marked by SNP rs1447295, is also associated with prostate cancer. The rs1447295 SNP is located nearby on the same arm of chromosome 8 and could be responsible for about 7% of prostate cancer cases in white men of north European descent. The old and the new susceptibility loci appear to act independently and confer increased   risk for all age groups studied, according to the investigators.

    A team of deCODE Genetics scientists, along with academic colleagues from the U.S., Iceland, Spain, and The Netherlands, also discovered a genetic variant on the same region of chromosome 8 that confers risk of prostate cancer. This new discovery emerges from the application of genome wide SNP association technologies to the company’s population genetics resources. The variant discovered by deCODE was identified through a genome-wide association scan of 4,500 Icelandic cases .

    The strongest association detected in the study was a variant identified last year by deCODE, but the team then applied its tools for constructing and testing haplotypes of multiple SNPs. This analysis identified a 14-marker haplotype and a closely correlated SNP not included in the company's earlier genome-wide scan. The variant was found in about 3% of controls and roughly twice as many prostate cancer patients and is suggestively linked to earlier age at onset.

    However, in an African American case-control cohort from Baltimore, the variant was found in about 30% of controls and 42% of patients, which could account for one quarter of prostate cancer cases among African Americans.
    deCODE intends to utilize these findings to develop a DNA-based test for the variants it has discovered. Both the NCI study and the deCODe study used the Illumina HumanHap300 Bead Chip.

    Along with these studies, researchers at the Keck School of Medicine of the University of Southern California (USC)  and Harvard Medical School identified seven genetic risk factors that predict prostate cancer. According to the study's findings, these risk factors are also clustered on the same region of the human genome on chromosome 8.

    According to the HMS/USC study, each of these genetic variants independently predict risk for prostate cancer, with the predictive strength varying depending on the variant. Almost all the risk factors were of highest frequency in African Americans.

    The study also produced novel biological findings. It revealed that each genetic contributor to prostate cancer risk is located outside of the coding regions of genes, in regions previously designated as junk DNA.

     



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