A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes
Menée à l'aide d'un modèle murin, cette étude identifie trois nouveaux gènes (CXCL14, ITGAX et LPCAT2) conférant une susceptibilité à une forme agressive de cancer de la prostate
Prostate cancer is a remarkably common disease, and in 2014 it is estimated that it will account for 27% of new cancer cases in men in the US. However, less than 13% those diagnosed will succumb to prostate cancer, with most men dying from unrelated causes. The tests used to identify men at risk of fatal prostate cancer are inaccurate, which leads to overtreatment, unnecessary patient suffering, and represents a significant public health burden. Many studies have shown that hereditary genetic variation significantly alters susceptibility to fatal prostate cancer, although the identities of genes responsible for this are mostly unknown. Here, we used a mouse model of prostate cancer to identify such genes. We introduced hereditary genetic variation into this mouse model through breeding, and used a genetic mapping technique to identify 35 genes associated with aggressive disease. The levels of three of these genes were consistently abnormal in human prostate cancers with a more aggressive disease course. Additionally, hereditary differences in these same three genes were associated with markers of fatal prostate cancer in men. This approach has given us unique insights into how hereditary variation influences fatal forms of prostate cancer.