Genetic Variants in the MicroRNA Machinery Gene GEMIN4 Are Associated with Risk of Prostate Cancer: A Case-control Study of the Chinese Han Population

Abstract

Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

“…However, we failed to find any association of rs442384, rs7813, rs486907 and rs1058205, although they were previously identified to be associated with PCa in European men (Agalliu et al, 2010;Parikh et al, 2010;Liu et al, 2012). The finding provided a helpful basis for seeking genetic etiology of prostate cancer specific to northern Han Chinese, considering the increasing incident rate of PCa.…”

“…The variants locating at 8q24 region (rs7837328, rs10505474 and * rs4242384) and rs7813, rs486907 and rs1058205 were reported strongly associated with PCa risk in Europeans, Americans and southern Asians), (Terada et al, 2008;Chen et al, 2009;Liu et al, 2009;Takata et al, 2010;Chen et al, 2010;Zheng et al, 2010;Liu et al, 2012.). However, consider the great difference of genetic background, environments and lifestyle between southern and northern Chinese, whether those variations also confer the PCa risk in Northern Chinese men remains unknown.…”

MicroRNA Theranostics in Prostate Cancer Precision Medicine

“…SNPs in the miRNA processing genes of the miRNA biogenesis pathway and in the miRNA binding sites, referred to as miRSNPs are known to contribute toward cancer risk. For example, the SNPs rs274034 and rs7813 located in GEMIN4 (gem nuclear organelle associated protein 4), one of the miRNA machinery genes were found to contribute to prostate cancer protection/risk in patients carrying the GC and TT variant genotypes (76 ). A large-scale analysis of genetic variants in miRNA binding sites identified 22 prostate cancer risk associated miRSNPs, the 2 most significant miRSNPs being KLK3 (kallikrein related peptidase 3) rs1058205 (TϾC) and VAMP8 (vesicle associated membrane protein 8) rs1010 (AϾG), which were targeted by miR-3162-5p and miR-370 -5p respectively in an allele specific manner (77 ).…”

MicroRNA polymorphisms as markers of risk, prognosis and treatment response in hematological malignancies

“…rs9611280 in TNRC6B is expected to affect splicing [26]. rs3744741 in GEMIN4 was also studied in other cancers and associations were found with reduced risk of more advanced prostate cancer [37] and better survival in renal cell carcinoma [38].…”