rs78943174

rs78943174 is a single-nucleotide polymorphism (SNP) found in the gene NAALADL2 that has been associated with prostate cancer aggressiveness as measured by the Gleason score. Prostate cancer is a type of cancer that forms in tissues of the prostate. It usually shows a slow growth and remains confined to the prostate gland not causing serious harm, but other types of prostate cancer can spread quickly and are aggressive. Aggressiveness can be measured with the Gleason score, a system which assigns a number from 2 to 10 to describe how abnormal the cells appear under a microscope. The higher the Gleason score is, the more aggressive the disease is. To evaluate disease aggressiveness, a multi-stage, case-only GWAS was conducted with a total of 12,518 prostate cancer cases of European ancestry. Regression models were fit taking the Gleason score as a quantitative trait and adjusting for age . rs78943174 (3q26.31) reached genome-wide significance (p = 4.18x10-8), with the C allele associated with higher Gleason score (more aggressive disease). The estimated coefficient for this SNP in the regression model is 0.289 with standard error of 0.053. The risk allele (C) frequency among cases is 0.985. The non-risk at rs78943174 is T. rs78943174 is intronic to the N-acetylated alpha-linked acidic dipeptidase-like2 (NAALADL2) gene, which is related to prostate-specific membrane antigen, a well characterized diagnostic indicator and potential drug target of prostate cancer. Variants in NAALADL2 have also been identified to be associated with Kawasaki disease. Two susceptibility loci identified for prostate cancer aggressiveness.