HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes

Hu, Yanling; Zhong, Donggen; Pang, Fang; Ning, Qiuyue; Zhang, Y Y; Li, G; Wu, Jianzhong; Mo, Zengnan

doi:10.4238/2013.april.25.4

Cited by 24 publications

(20 citation statements)

References 30 publications

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“…This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PrCa [61]. It may also be involved in PrCa development via modulating androgenic hormone effects [62]. Consistent with our result, a previous eQTL analysis also reported the eQTL association for rs4430796-HNF1B only in tumor-adjacent, histologically benign prostate tissue but not in tumors [38].…”

Section: Plos Geneticssupporting

confidence: 91%

“…One pair (rs12653946-IRX4) was identified in both tumor and tumor-adjacent benign samples, one (rs4430796-HNF1B) was only identified in adjacent benign samples, and the last in tumors only (rs11135910-EBF2). Interestingly, all three eGenes encode transcription factors and are believed to be tumor suppressor genes [59][60][61][62][63]. The association of rs1265394 and IRX4 transcript has been reported previously in Japanese and European populations [59,64].…”

Section: Plos Geneticsmentioning

confidence: 71%

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DNA methylation and cis-regulation of gene expression by prostate cancer risk SNPs

Dai

Wang

et al. 2020

PLoS Genet

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Genome-wide association studies have identified more than 100 SNPs that increase the risk of prostate cancer (PrCa). We identify and compare expression quantitative trait loci (eQTLs) and CpG methylation quantitative trait loci (meQTLs) among 147 established PrCa risk SNPs in primary prostate tumors (n = 355 from a Seattle-based study and n = 495 from The Cancer Genome Atlas, TCGA) and tumor-adjacent, histologically benign samples (n = 471 from a Mayo Clinic study). The role of DNA methylation in eQTL regulation of gene expression was investigated by data triangulation using several causal inference approaches, including a proposed adaptation of the Causal Inference Test (CIT) for causal direction. Comparing eQTLs between tumors and benign samples, we show that 98 of the 147 risk SNPs were identified as eQTLs in the tumor-adjacent benign samples, and almost all 34 eQTL identified in tumor sets were also eQTLs in the benign samples. Three lines of results support the causal role of DNA methylation. First, nearly 100 of the 147 risk SNPs were identified as meQTLs in one tumor set, and almost all eQTLs in tumors were meQTLs. Second, the loss of eQTLs in tumors relative to benign samples was associated with altered DNA methylation. Third, among risk SNPs identified as both eQTLs and meQTLs, mediation analyses suggest that over two-thirds have evidence of a causal role for DNA methylation, mostly mediating genetic influence on gene expression. In summary, we provide a comprehensive catalog of eQTLs, meQTLs and putative cancer genes for known PrCa risk SNPs. We observe that a substantial portion of germline eQTL regulatory mechanisms are maintained in the tumor development, despite somatic alterations in tumor genome. Finally, our mediation analyses illuminate the likely intermediary role of CpG methylation in eQTL regulation of gene expression.

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Section: Plos Geneticssupporting

confidence: 91%

Section: Plos Geneticsmentioning

confidence: 71%

DNA methylation and cis-regulation of gene expression by prostate cancer risk SNPs

Dai

Wang

et al. 2020

PLoS Genet

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“…But both POU5F1 and HNF1B play important roles in embryonic development, and they boost each other’s importance. HNF1B has also recently been shown to modulate the effects of growth hormones and tumor progression 27 .…”

Section: Resultsmentioning

confidence: 99%

Selecting causal genes from genome-wide association studies via functionally coherent subnetworks

et al. 2014

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While genome-wide association (GWA) studies have linked thousands of loci to human diseases, the causal genes and variants at these loci generally remain unknown. Although investigators typically focus on genes closest to the associated polymorphisms, the causal gene is often more distal. Relying on the literature to help prioritize additional candidate genes at associated loci can draw attention away from less-characterized causal genes. Here we describe a strategy that uses genome-scale ‘co-function’ networks to identify sets of mutually functionally related genes spanning multiple GWA loci. Using associations from ~100 GWA studies covering ten cancer types, this approach outperforms the common alternative strategy in ranking known cancer genes. The strategy’s power grows with more GWA loci, offering an increasing opportunity to elucidate causes of complex human disease.

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“…7 A conditional liver-specific inactivation of the HNF1β gene resulted in abnormalities of the gallbladder and IHBDs and paucity of the small IHBD. 7 HNF1β expression has been reported in prostatic, 26 ovarian, 27 and renal cancers 28 but not in melanomas or breast, colorectal, lung, or pancreatic cancers. 29 Although a study reported HNF1β expression in human HCCs, 15 its clinicopathological implications remained largely unclear.…”

Section: Discussionmentioning

confidence: 98%

Expression of Bile Duct Transcription Factor HNF1β Predicts Early Tumor Recurrence and Is a Stage-Independent Prognostic Factor in Hepatocellular Carcinoma

Yuan

Lai

Hsu

et al. 2014

Journal of Gastrointestinal Surgery

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HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes

Cited by 24 publications

References 30 publications

DNA methylation and cis-regulation of gene expression by prostate cancer risk SNPs

DNA methylation and cis-regulation of gene expression by prostate cancer risk SNPs

Selecting causal genes from genome-wide association studies via functionally coherent subnetworks

Expression of Bile Duct Transcription Factor HNF1β Predicts Early Tumor Recurrence and Is a Stage-Independent Prognostic Factor in Hepatocellular Carcinoma

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