Genome‐Wide 3′‐UTR Single Nucleotide Polymorphism Association Study Identifies Significant Prostate Cancer Risk‐Associated Functional Loci at 8p21.2 in Chinese Population

Zhang, Ning; Huang, Da; Jiang, Guangliang; Chen, Siteng; Ruan, Xiaohao; Chen, Haitao; Huang, Jingyi; Liu, Ao; Zhang, Wenhui; Lin, Xiaoling; Wu, Yishuo; Zhang, Qin; Li, Jing; Tsu, James Hok‐Leung; Wei, Gong‐Hong; Na, Rong

doi:10.1002/advs.202201420

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…A few years ago, different studies have shown the impact of 3’UTR variants on the expression and susceptibility to cancer development. 18 , 28 , 29 In this study, we were interested in exploring the impact of 3’UTR variants on the gene expression of BRCA1 . In fact, BRCA1, as well as BRCA2, have an important role in the biology of the cell, especially in tumor microenvironment in BC.…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of BRCA1 3’UTR Variants Predisposing to Breast Cancer

Sierra-Díaz,

Cabrera,

Gonzalez-Vasquez

et al. 2024

TACG

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Purpose Breast Cancer (BC) is the main female cancer diagnosed worldwide, and it has been described that few genes, such as BRCA1 , have a high penetrance for this type of cancer. In this manuscript, we were interested in evaluating the effect of 3’UTR variants on BRCA1 expression. Patients and Methods To accomplish this objective, Whole Exome Sequencing (WES) data of 400 patients with unselected BC was used to filter variants located in the region of interest of BRCA1 gene, finding two of them (c.*36C>G and c.*369_373del). miRGate and miRanda in silico tools were used to predict microRNA (miRNA) interaction. Results The two variants (c.*36C>G, c.*369_373del) were predicted to affect miRNA interaction. After cloning of BRCA1 3’UTR into pMIR-Report vector, the construct was transfected into two BC cell lines (MDA-MB-231 and MCF-7), and the variant c.*36C>G evidenced overexpression of reporter gene luciferase, showing that the transcript was not being degraded by the miRNA in MDA-MB-231 cells. Conclusion The variant seems to protect against Triple Negative BC probably due to the expression level of miRNA in this particular cell line (MDA-MB-231). This is consistent with the clinical history of the patients who harbor BC Hormone Receptors positive (HR+).

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Section: Discussionmentioning

confidence: 99%

Functional Analysis of BRCA1 3’UTR Variants Predisposing to Breast Cancer

Sierra-Díaz,

Cabrera,

Gonzalez-Vasquez

et al. 2024

TACG

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“…The conceptual framework and the three MR assumptions of the current study are illustrated in Figure 1; briefly: (i) instrumental variables (single nucleotide polymorphisms [SNP]) are truly associated with the behavioral factors, (ii) SNPs are unrelated to the confounders on the behaviors-PCa nexus, (iii) SNPs affect PCa only via behavioral factors. SNPs were obtained from summary data from reported GWAS and a GWAS cohort of PCa in the East Asian population (Chinese) [13,14]. The study was reported in accordance with the STROBE-MR guidelines [15].…”

Section: Methodsmentioning

confidence: 99%

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study

Zhan

Ruan

Wang

et al. 2023

Biology

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Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. Methods: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). Results: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09–3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01–1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00–1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88–0.96, p = 0.001) was a protective factor for PCa. Conclusions: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.

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“…SNPs in the introns can affect RNA splicing and can promote or disrupt the binding and function of long non-coding RNAs (lncRNAs) ( 91 – 93 ). SNPs located in the 5’- and 3’- untranslated regions (UTRs) may affect protein translation and miRNA-dependent gene silencing ( 94 , 95 ). These aforementioned mechanisms may potentially impact the expression level of MRGPRX2 and lead to the production of variants with different properties.…”

Section: Mrgprx2 Triggering and Its Individual Variability As An Exam...mentioning

confidence: 99%

Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link

Porebski,

Dziadowiec,

Rybka

et al. 2024

Front. Immunol.

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Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.

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Genome‐Wide 3′‐UTR Single Nucleotide Polymorphism Association Study Identifies Significant Prostate Cancer Risk‐Associated Functional Loci at 8p21.2 in Chinese Population

Cited by 5 publications

References 30 publications

Functional Analysis of BRCA1 3’UTR Variants Predisposing to Breast Cancer

Functional Analysis of BRCA1 3’UTR Variants Predisposing to Breast Cancer

Causal Effects of Modifiable Behaviors on Prostate Cancer in Europeans and East Asians: A Comprehensive Mendelian Randomization Study

Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link

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