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RNASEL、MSR1和ELAC2单核苷酸多态性与前列腺癌风险中基因表达之间的关联。

Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk.

作者信息

Alvarez-Cubero Maria Jesus, Pascual-Geler Manrique, Martinez-Gonzalez Luis Javier, Expósito Ruiz Manuela, Saiz Maria, Cozar Jose Manuel, Lorente Jose Antonio

机构信息

Liquid biopsy and metastasis research group and Genomic Unit, GENyO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.

Service of Urology, University Hospital Virgen de las Nieves, Granada, Spain.

出版信息

Urol Oncol. 2016 Oct;34(10):431.e1-8. doi: 10.1016/j.urolonc.2016.05.018. Epub 2016 Jun 16.

Abstract

BACKGROUND

There is contradictory evidence of the effects that environmental factors-dietary habits (ingestion rates of red meat, soy products, fish, etc.) and work environment (exposure to metals, pesticides, several toxic products, etc.)-and KLK3, AR, RNASEL, MSR1, and ELAC2 expression patterns have on prostate cancer (PCa). In our study, we investigated the potential association between KLK3, AR, RNASEL, MSR1, and ELAC2 polymorphisms, expression patterns, exposure to environmental factors, and PCa in a Spanish cohort. Blood and fresh tissue samples were collected from 322 subjects with prostate-specific antigen (PSA)>4ng/ml to determine their genotypes (RNASEL, MSR1, and ELAC2) and assess messenger ribonucleic acid expression levels (by quantitative amplification testing).

MAIN FINDINGS

Among clinical parameters, a 63.6% of patients with CC variants in rs11545302 (ELAC2) had PSA>20ng/ml (P = 0.008), and rs486907 (RNASEL), with 52.8% of patients with CT variants with Gleason score>7. Regarding TNM stage, patients with GG variants, rs4792311 (ELAC2) generally had stage 1 tumors. Genetic expression analysis revealed RNASEL (P = 0.007) was underexpressed in PCa tissue, whereas KLK3 (P = 0.041) was overexpressed. As to environmental factors, the intake of dried fruits (P = 0.036) and practice of sports (P = 0.024) revealed an effect in PCa. Moreover, environmental factors were observed to affect gene expression patterns. Thus, RNASEL (P = 0.018) and ELAC2 (P = 0.023) were found to be underexpressed in patients who ate processed foods frequently; MSR1 (P = 0.024) and AR (P = 0.004) were underexpressed in patients who did not practice sports; and KLK3 (P = 0.039; P = 0.046) underexpressed in patients exposed to dust and toxic products.

CONCLUSIONS

This is the first study to analyze the correlation between RNASEL, MSR1, and ELAC2 genotypes and messenger ribonucleic acid expression in PCa. RNASEL and KLK3 show different expression patterns in normal vs. tumor tissue, which supports their reported relevance in human cancer. The results obtained confirm that RNASEL plays a crucial role in PCa. Environmental factors such as exercise, exposure to toxic agents, and intake of processed foods are associated with PCa.

摘要

背景

关于环境因素——饮食习惯(红肉、豆制品、鱼类等的摄入量)和工作环境(接触金属、农药、多种有毒产品等)——以及激肽释放酶3(KLK3)、雄激素受体(AR)、核糖核酸酶L(RNASEL)、巨噬细胞清道夫受体1(MSR1)和2-酯酶A2(ELAC2)的表达模式对前列腺癌(PCa)的影响,证据相互矛盾。在我们的研究中,我们调查了西班牙一个队列中KLK3、AR、RNASEL、MSR1和ELAC2基因多态性、表达模式、环境因素暴露与PCa之间的潜在关联。从322名前列腺特异性抗原(PSA)>4ng/ml的受试者中采集血液和新鲜组织样本,以确定他们(RNASEL、MSR1和ELAC2)的基因型,并评估信使核糖核酸表达水平(通过定量扩增检测)。

主要发现

在临床参数中,rs11545302(ELAC2)中CC变异的患者中有63.6%的PSA>20ng/ml(P = 0.008),而rs486907(RNASEL)中CT变异的患者中有52.8%的 Gleason评分>7。关于TNM分期,rs4792311(ELAC2)中GG变异的患者通常为1期肿瘤。基因表达分析显示,RNASEL(P = 0.007)在PCa组织中表达不足,而KLK3(P = 0.041)表达过度。至于环境因素,干果摄入量(P = 0.036)和体育锻炼(P = 0.024)显示对PCa有影响。此外,观察到环境因素会影响基因表达模式。因此,经常食用加工食品的患者中,RNASEL(P = 0.018)和ELAC2(P = 0.023)表达不足;不进行体育锻炼的患者中,MSR1(P = 0.024)和AR(P = 0.004)表达不足;接触灰尘和有毒产品的患者中,KLK3(P = 0.039;P = 0.046)表达不足。

结论

这是第一项分析PCa中RNASEL、MSR1和ELAC2基因型与信使核糖核酸表达之间相关性的研究。RNASEL和KLK3在正常组织与肿瘤组织中表现出不同的表达模式,这支持了它们在人类癌症中所报道的相关性。获得的结果证实RNASEL在PCa中起关键作用。运动、接触有毒物质和食用加工食品等环境因素与PCa相关。

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