P30: Genetic aspects of prostate cancer development

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• 作者：N. Tarasenko^a ; ; L. Spirina^b ; ^c ; E. Usynin^b ; A. Gorbunov^b
• 刊名：European Journal of Cancer Supplements
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：13
• 期：1
• 页码：60-61
• 全文大小：45 K

文摘

Prostate cancer is presented as the most commonly diagnosed cancer in men. According to statistical reports, every 6th man have the prostate cancer and out of them every 34th man will have the castrate-resistant form of disease. The existing clinical and prognostic factors can explain cancer outcome in small part of patients. The prediction of individual prostate cancer prognosis and anticancer therapy effect are the main goals of the advanced personalized therapy. The modern genetic technologies development (GWAS, genome sequencing) will allow to find the effective prognostic markers of prostate cancer.

During the GWAS performance it was found loci associated with the prostate cancer development. The analysis of on-line base “A Catalog of Published Genome-Wide Association Studies” (www.genome.gov), containing the full information of genome associative investigations as well as 30 studies of prostate cancer, revealed the associations of 159 SNPs in different ethnic groups of patients (Caucasian, Asian and Negroid). 86 SNPs among them located in 77 genes, 65 SNPs – had the intergenic localization. The GWAS performance in prostate cancer Caucasian patients have found the associations of 76 SNPs in 72 genes and 65 SNPs in intergenic regions. SNPs in genes were located in 81.4% of cases in introns, in 5.3% – in other locations as well as missense changes (near 5′-UTR, ncRNA). It was obtained 30 markers related to disease of different ethnic groups of patients in GWAS. 17 SNPs among them (rs10187424, rs6545977, rs7584330, rs10936632, rs651164, rs12155172, rs1512268, rs4242384, rs3123078, rs11199874, rs7127900, rs7130881, rs10875943, rs4775302, rs5759167, rs1327301, rs5919432) had the intergenic localization, 12 SNPs (rs1465618, rs12621278, rs17181170, rs6763931, rs17021918, rs12500426, rs7679673, rs2121875, rs2242652, rs6465657, rs7501939, rs1859962) were located in introns and 1 SNP (rs130067) – in exon.

It was revealed the overfilled genome region was 8q24.21. Association with prostate cancer was found with 17 SNPs. 8 SNPs had the intergenic localization: SRRM1P1–CCAT1 (rs16901979, rs12682344, rs6983561, rs10505483) and CASC8–CASC11 (rs10090154, rs4242384, rs7837688, rs4242382); 9 SNPs – intragenic location: PRNCR1 (rs1016343, rs1456315, rs13254738, rs13252298), LOC101930033 (rs445114, rs16902094, rs10505477), CCAT2 (rs6983267), CASC8 (rs1447295).

The early development of the disease was associated with the 9 SNPs: 4 SNPs were located in genes, 5 SNPs had the intergenic localization. It was noted among 9 SNPs 4 markers were in 11q13.3 region (rs7127900, rs7126629, rs7931342, rs11228583). 5 markers (rs6983267, rs10993994, rs7127900, rs7931342, rs17632542) have found in prostate cancer patients and in group of patients with early development.

The 7 SNPs had the association with PSA level (rs16856139, rs12409639, rs10993994, rs3213764, rs1058205, rs1354774, rs2735839). 1 SNP among them was located intergenic region (KLK3–KLK2 rs2735839), 6 SNPs – were in genes (SLC45A3 rs16856139, rs12409639, MSMB rs10993994, ATF7I rs3213764, KLK3 rs1058205, KLKP1 rs1354774). 2 SNPs from 7 (rs10993994, rs2735839) had the relation to PSA level and to prostate cancer patients. Polymorphic variant rs10993994, located near 5′-UTR MSMB gene, had the associations with prostate cancer patients, patients with early start of disease and with PSA level.

In conclusion, the search of genetic markers of prostate cancer development is actual inmodern oncology. These data will allow to form the groups of patients with different outcome and prognosis and perform the personalized therapy for every patient.