A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer

Stegeman, Shane; Amankwah, Ernest K.; Klein, Kerenaftali; O’Mara, Tracy A.; Kim, Donghwa; Lin, Hui‐Yi; Permuth-Wey, Jennifer; Sellers, Thomas A.; Srinivasan, Srilakshmi; Eeles, Rosalind; Easton, Doug; Kóte-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David E.; Pharoah, Paul D.P.; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen N.; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Teixeira, Manuel R.; Spurdle, Amanda B.; Clements, Judith A.; Park, Jong Y.; Batra, Jyotsna

doi:10.1158/2159-8290.cd-14-1057

Cited by 55 publications

(35 citation statements)

References 50 publications

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“…For patients with early-stage cervical squamous cell carcinoma, miR-3162-5p was a member of a six-miRNA panel that was able to predict lymph node metastasis with an AUC of 0.9320 [39]. In prostate cancer, a probable role of miR-3162-5p in the mechanism underlining the increased prostate cancer risk with the kallikrein-related peptidase 3 (KLK3) rs1058205 miRSNP T-allele has been demonstrated [40]. Furthermore, in a recent study, the increased expression of miR-3162-5p in prostate tumor tissues has been associated with a higher Gleason grade; thus, indicating the possible use of miR-3162-5p in stratifying patients who are at risk of developing aggressive prostate cancer [41].…”

Section: Discussionmentioning

confidence: 99%

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Loke

Munusamy

Koh

et al. 2019

Cancers

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Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

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Section: Discussionmentioning

confidence: 99%

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Loke

Munusamy

Koh

et al. 2019

Cancers

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“…Genetic variants in miRNA regulome may affect miRNA transcription and regulation of targeted genes, and finally contribute to the development of complex traits and diseases. Some GWAS‐based studies have comprehensively investigated the associations of single nucleotide polymorphisms (SNPs) in miRNA regulome with human traits and diseases . Bulik‐Sullivan et al .…”

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confidence: 99%

“…Some GWAS-based studies have comprehensively investigated the associations of single nucleotide polymorphisms (SNPs) in miRNA regulome with human traits and diseases. [17][18][19][20][21] Bulik-Sullivan et al systematically cataloged trait/disease-associated SNPs in miRNA promoter regions and identified a variant in the promoter of the miRNA let-7 linked with human height variation. 17 Williamson et al revealed that SNPs associated with miRNA expression were enriched in the significant GWAS signals of some special diseases.…”

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confidence: 99%

A polymorphism in miR‐1262 regulatory region confers the risk of lung cancer in Chinese population

Xie

Chen

Zhu

et al. 2017

Intl Journal of Cancer

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It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis.

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“…The 'winner's curse', the observation that effect sizes are often larger in the populations in which they are discovered, may be one reason why some SNPs failed to replicate, and why ORs were generally smaller in our cohort than previously found [27]. Previous studies have shown the utility of including functional evaluation, in an attempt to identify candidate risk loci below currently accepted statistical levels of genome-wide significance [28]. Functional characterization of the variants described here remains to be done.…”

Section: Discussionmentioning

confidence: 80%

Profile of common prostate cancer risk variants in an unscreened Romanian population

Iordache

Mateș

Gunnarsson

et al. 2017

J Cellular Molecular Medi

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To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10−4), rs7929962 at 11q13.3 (P = 2.7 × 10−4) and rs9364554 at 6q25.2 (P = 4.7 × 10−4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10−8) but 807 markers had P‐values <1 × 10−4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.

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A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer

Cited by 55 publications

References 50 publications

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

A polymorphism in miR‐1262 regulatory region confers the risk of lung cancer in Chinese population

Profile of common prostate cancer risk variants in an unscreened Romanian population

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