Nat Commun:日本人群全基因组关联分析鉴定了12个新的前列腺癌易感位点

2019-10-17 AlexYang MedSci原创

全基因组关联分析(GWAS)已经鉴定了大约170个与前列腺癌(PCa)风险相关的位点,但是其中的大多数是在欧洲人群中鉴定的。最近,有研究人员利用GWAS和复制研究在一个大的日本群体(9960个案例和83943个男性对照)中鉴定了与PCa风险相关的新的易感位点。研究总共鉴定出了12个新的PCa位点,包括rs1125927 (TMEM17,P=3.95×10-16), rs73862213 (GATA

全基因组关联分析(GWAS)已经鉴定了大约170个与前列腺癌(PCa)风险相关的位点,但是其中的大多数是在欧洲人群中鉴定的。最近,有研究人员利用GWAS和复制研究在一个大的日本群体(9960个案例和83943个男性对照)中鉴定了与PCa风险相关的新的易感位点。

研究总共鉴定出了12个新的PCa位点,包括rs1125927 (TMEM17,P=3.95×10-16), rs73862213 (GATA2,P=5.87×10-23), rs77911174 (ZMIZ1,P=5.28×10-20)和rs138708(SUN2, P=1.13×10-15),其中的7个位点在欧洲人群中具有极低的小等位基因频率。更多的是,研究人员对日本PCa患者多基因风险利用82个SNPs进行了分层,该82个SNPs在他们的研究与PCa风险显著相关,并且发现早期起始案例和具有家族PCa历史的案例在遗传高风险人群中富集。

最后,研究人员指出,他们的研究为PCa的遗传机制提供了重要的认识,并促进了日本人群中PCa的分线分层。

原始出处:

Ryo Takata, Atsushi Takahashi, Masashi Fujita et al. 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population. Nat Commun. 27 Sep 2019

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    2020-07-21 liuli5079
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    2019-11-24 wshxjq
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    2020-03-14 liye789132251
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    2019-10-17 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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肿瘤的发生可以由种系、环境和随机因素诱发。但这些因素是怎样互作产生肿瘤的分子表型的仍旧未知。最近,有研究人员在589个局部前列腺肿瘤中量化了种系多样性对体细胞表观基因组的影响。研究发现,倾向性风险位点影响了肿瘤的表观基因组,揭示了癌症易感性的机制。研究人员总共见顶了1178个位点与肿瘤组织中甲基化的改变有关,而不是非恶性肿瘤组织。这些肿瘤甲基化数量性状位点能够影响染色质结构以及RNA和蛋白的丰度。

Cell Death & Disease:前列腺癌中靶向Wnt/EZH2/microRNA-708信号途径能够抑制神经纤维瘤分化

前列腺癌(PC)的去势抵抗性与PC腔细胞分化成为激素激素难治性神经内分泌(NE)细胞有关。然而,控制致死性NE前列腺癌(NEPC)的机制仍旧不清楚。最近,有研究人员调查了前列腺癌恶性肿瘤到NEPC转化过程中的机制。研究发现,microRNA miR-708参与了NE分化,并在NEPC细胞和肿瘤活检样本中下调。miR-708能够靶向Sestrin-3来抑制叉头转录因子(FOXO1)的磷酸化,从而导致

Sci Rep:前列腺癌细胞中AR无差异抗雄激素抗性驱使因子分析

二代抗雄激素类药物抑制雄激素受体(AR)是转移去势抵抗性前列腺癌(mCRPC)的标准治疗方法,但是不可避免的会导致抗性的产生。自从高效AR信号抑制剂的使用,大于20%的mCRPC的患者发展为不依赖AR抗性机制疾病。最近,有研究人员开发了2个抗雄激素药物和不依赖AR活性的去势抵抗性前列腺癌细胞模型,尽管模型中AR表达强烈(AR无差异)。这些模型对所有当今的AR信号抑制剂存在抗性。研究发现,这2个细胞

Nat Commun:PTEN-ARID4B-PI3K途径鉴定了PTEN缺陷前列腺癌对ARID4B的依赖性

在前列腺癌中,PTEN经常发生变异。PTEN的肿瘤抑制子功能归结于其脂肪磷酸化活性且能够拮抗PI3K的作用。最近,有研究人员报道了PTEN-ARID4B-PI3K途径,其中PTEN能够抑制ARID4B的表达,而ARID4B是PI3K亚单元基因PIK3CA和PIK3R2的转录激活因子,且亚单元基因PIK3CA和PIK3R2对PI3K/AKT途径的激活是非常关键的。ARID4B和组蛋白H1结合到PIK

Sci Rep:亚洲前列腺癌患者中周围血栓栓塞性血管疾病与雄激素阻断治疗相关性分析

最近,有研究人员在前列腺癌(PCa)患者中调查了血栓栓塞的血管疾病在雄激素阻断治疗(ADT)后的风险情况。研究包括了24464名在2000-2008年新诊断为PCa的患者,且是通过纵向医疗保险数据库获得数据。所有的的PCa患者分成了2组:ADT组和非ADT组。ADT治疗的患者再分成手术去势组,化学去势组和单独抗雄激素组。研究人员通过依赖时间变量的多重Cox比例风险回归评估了肺栓塞(PE)、外周动脉

Cell Death & Disease:前列腺癌中PAX5能够诱导IDH1-AS1上调来促进肿瘤的生长

前列腺癌(PCa)是世界范围内影响男性健康的主要恶性肿瘤之一。长非编码RNAs(lncRNAs)是一类长的转录本,并且报道在恶性肿瘤中是必要的调控因子。IDH1反义RS1(IDH1-AS1)是一个lncRNA,并能与基因互作来调控瓦博格效应。然而,其在PCa致瘤中的作用和机制仍旧不清楚。最近,有研究人员探索了IDH1-AS1在PCa肿瘤生长中的作用。研究发现,IDH1-AS1的表达在PCa样本和细