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  • TMPRSS2 LINKED EXOCRINE NETWORK IN PROSTATE CANCER SUSCEPTIBILITY GWAS LOCI

    April 2, 2015.  Some cancer susceptibility loci may be expected to share genes/mechanisms.  We recently analyzed breast cancer susceptibility loci, and were curious to see if other cancer risk GWAS showed overlapping genes/loci.  Because breast cancer risk genes BRCA1 and BRCA2 also confer increased risk for prostate cancer, we took a quick look at prostate cancer risk data. Twenty three loci were published last year in Nature Genetics "A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer". Of 56 breast cancer loci, we noted only a single overlapping locus on Chromosome 1 containing PEX14, APITD1, DFFA, PGD, CORT, suggesting the majority of the cancer susceptibility mechanisms were distinct between the two tumor types.

    To further explore candidate biology in the Prostate Cancer GWAS, 67 genes near the 23 loci were plotted on a bathymetry plot (Figure).

    Among several network clusters, the most prominent contained TMPRSS2, half of an oncogenic fusion partner (TMPRSS2-ERG) common in prostate cancer.  Other genes in the network MARVELD3, TTC9 (and neighbor MAP3K9), GOLPH3L, MYO6, HTR3A, SIX4 all exhibit prominent salivary and/or exocrine gland expression, including TMPRSS2 which is prostate specific.  While there is more to learn about the biology of this cluster, we present it here for the prostate cancer and GWAS community.