Systematic evaluation of bladder cancer risk-associated single-nucleotide polymorphisms in a chinese population

2012 ◽  
Vol 52 (11) ◽  
pp. 916-921 ◽  
Author(s):  
Zhicheng Ma ◽  
Qingfeng Hu ◽  
Zhuo Chen ◽  
Sha Tao ◽  
Lindsay Macnamara ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
Systematic Evaluation ◽  
Nucleotide Polymorphisms ◽  
Bladder Cancer Risk ◽  
Single Nucleotide

scholarly journals Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristina M. Jordahl ◽  
Amanda I. Phipps ◽  
Timothy W. Randolph ◽  
Lesley F. Tinker ◽  
Rami Nassir ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Bladder Cancer Risk ◽  
Single Nucleotide ◽  
Cpg Sites

Abstract Background Though bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL). Methods Among 412 bladder cancer cases and 424 controls from the Women’s Health Initiative (WHI), we assessed whether the effects of these SNPs on bladder cancer are mediated through proximal DNA methylation changes in pre-diagnostic blood at mQTL-associated CpG sites, which we refer to as natural indirect effects (NIEs). We used a multiple-mediator mediation model for each of the four mQTL adjusted for matching variables and potential confounders, including race/ethnicity, smoking status, and pack-years of smoking. Results While not statistically significant, our results suggest that substantial proportions of the modest effects of rs401681 (ORNIE = 1.05, 95% confidence interval (CI) = 0.89 to 1.25; NIE percent = 98.5%) and rs2294008 (ORNIE = 1.10, 95% CI = 0.90 to 1.33; NIE percent = 77.6%) on bladder cancer risk are mediated through differential DNA methylation at nearby mQTL-associated CpG sites. The suggestive results indicate that rs2294008 may affect bladder cancer risk through a set of genes in the lymphocyte antigen 6 family, which involves genes that bind to and modulate nicotinic acetylcholine receptors. There was no suggestive evidence supporting mediation for rs8102137 and rs798766. Conclusions Though larger studies are necessary, the methylation changes associated with rs401681 and rs2294008 at mQTL-associated CpG sites may be relevant for bladder carcinogenesis, and this study demonstrates how multi-omic data can be integrated to help understand the downstream effects of genetics variants.

scholarly journals Joint effects of single nucleotide polymorphisms in P53BP1 and p53 on breast cancer risk in a Chinese population

2005 ◽  
Vol 27 (4) ◽  
pp. 766-771 ◽  
Author(s):  
Hongxia Ma ◽  
Zhibin Hu ◽  
Xiangjun Zhai ◽  
Shui Wang ◽  
Xuechen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Joint Effects

scholarly journals Renin-Angiotensin System Single Nucleotide Polymorphisms Are Associated with Bladder Cancer Risk

2021 ◽  
Vol 28 (6) ◽  
pp. 4702-4708
Author(s):  
Maria Samara ◽  
Maria Papathanassiou ◽  
Ioanna Farmakioti ◽  
Maria Anagnostou ◽  
Maria Satra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Renin Angiotensin System ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Ras Gene ◽  
Single Nucleotide ◽  
Angiotensin System ◽  
Renin Angiotensin

The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC. Peripheral blood samples from 73 patients with T1 urothelial BC (66 men, seven women) and an equal number of healthy subjects (control group) were collected. The TT genotype of the REN rs12750834 SNP (OR: 2.8 [1.3–6.05], p = 0.008) and to a lesser extent the presence of the T allele (OR: 2.3 [1.2–4.48], p = 0.01) conferred a higher risk of BC. The highest risk for BC within SNP carriers of the RAS system was associated with the presence of the CC genotype (OR: 17.6 [7.5–41.35], p < 0.001) and C allele (OR: 17.7 [8.8–35.9], p < 0.001) of the ANG rs699 SNP. The presence of the AT2R rs11091046 SNP, particularly the AA genotype, was associated with a protective effect against developing BC (OR: 0.268 [0.126–057], p < 0.001). In conclusion, these results support the clinical utility of RAS gene SNPs AT2R rs11091046, REN rs12750834, and ANG rs699 in the genetic cancer risk assessment of patients and families with BC.

scholarly journals Single-Nucleotide Polymorphisms Sequencing Identifies Candidate Functional Variants at Prostate Cancer Risk Loci

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 547 ◽  
Author(s):  
Peng Zhang ◽  
Lori S. Tillmans ◽  
Stephen N. Thibodeau ◽  
Liang Wang
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Single Nucleotide Polymorphisms ◽  
Protein Binding ◽  
Prostate Cancer Risk ◽  
Sequencing Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Variants ◽  
Dependent Protein

Genome-wide association studies have identified over 150 risk loci that increase prostate cancer risk. However, few causal variants and their regulatory mechanisms have been characterized. In this study, we utilized our previously developed single-nucleotide polymorphisms sequencing (SNPs-seq) technology to test allele-dependent protein binding at 903 SNP sites covering 28 genomic regions. All selected SNPs have shown significant cis-association with at least one nearby gene. After preparing nuclear extract using LNCaP cell line, we first mixed the extract with dsDNA oligo pool for protein–DNA binding incubation. We then performed sequencing analysis on protein-bound oligos. SNPs-seq analysis showed protein-binding differences (>1.5-fold) between reference and variant alleles in 380 (42%) of 903 SNPs with androgen treatment and 403 (45%) of 903 SNPs without treatment. From these significant SNPs, we performed a database search and further narrowed down to 74 promising SNPs. To validate this initial finding, we performed electrophoretic mobility shift assay in two SNPs (rs12246440 and rs7077275) at CTBP2 locus and one SNP (rs113082846) at NCOA4 locus. This analysis showed that all three SNPs demonstrated allele-dependent protein-binding differences that were consistent with the SNPs-seq. Finally, clinical association analysis of the two candidate genes showed that CTBP2 was upregulated, while NCOA4 was downregulated in prostate cancer (p < 0.02). Lower expression of CTBP2 was associated with poor recurrence-free survival in prostate cancer. Utilizing our experimental data along with bioinformatic tools provides a strategy for identifying candidate functional elements at prostate cancer susceptibility loci to help guide subsequent laboratory studies.

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