Development of a Custom NGS Panel for the Determination of Bladder Cancer Risk

2021 ◽  
Author(s):  
Imen Hemissi ◽  
SAMI BOUSETTA ◽  
Hamza Dallali ◽  
Faycel Hellal ◽  
Geoffroy Durand ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bladder Cancer ◽  
Genetic Risk ◽  
Reference Group ◽  
Genetic Risk Factors ◽  
Ion Torrent ◽  
Targeted Next Generation Sequencing ◽  
Increased Risk ◽  
Assessment And Treatment ◽  
Underlying Mechanisms

Abstract BackgoundBladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The objective of this study was to design a panel that evaluates the role of some selected variants in BCa susceptibility. We are also interested in studying the interaction between environmental and genetic risk factors.MethodsThe case/controls cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) is composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). ResultsWe have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR=2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non–smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A>G), ARNT/ rs1889740 (C>T) or GSTA4/rs17614751 (G to A) were respectively at 2.775, 3.069 and 6.608 –folds increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa class. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. ConclusionsThe determined association between genetic variations in BCa and environmental factors, as well as the effect of studied pathway SNPs in comparison with environmental exposition may provide urologists additional genetic information that may help for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.

Lifestyle and sociodemographic risk factors for gastroschisis: a systematic review and meta-analysis

2020 ◽  
Vol 105 (8) ◽  
pp. 756-764 ◽  
Author(s):  
Silvia Baldacci ◽  
Michele Santoro ◽  
Alessio Coi ◽  
Lorena Mezzasalma ◽  
Fabrizio Bianchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Illicit Drugs ◽  
Meta Analysis ◽  
Genetic Risk Factors ◽  
Epidemiological Studies ◽  
Black Mothers ◽  
Increased Risk ◽  
Sociodemographic Risk ◽  
Meta Analyses

BackgroundGastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring.ObjectiveTo systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis.MethodsLiterature from PubMed, EMBASE and Scopus was searched for the period 1990–2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model.ResultsWe identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed.ConclusionsExposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended.PROSPERO registration numberCRD42018104284.

scholarly journals Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia

2008 ◽  
Vol 192 (6) ◽  
pp. 424-428 ◽  
Author(s):  
Olga O. Yevtushenko ◽  
Stephen J. Cooper ◽  
Ryan O'Neill ◽  
Jennifer K. Doherty ◽  
Jayne V. Woodside ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Drug Treatment ◽  
Genetic Polymorphisms ◽  
Genetic Risk ◽  
Antipsychotic Drugs ◽  
Genetic Risk Factors ◽  
Metabolic Disturbances ◽  
Genotype Combination ◽  
Increased Risk

BackgroundObesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors.AimsTo investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia.MethodPatients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT2C receptor −759C/T and leptin −2548A/G).ResultsNeither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine.ConclusionsThe findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

scholarly journals Clusterin accumulates in synapses in Alzheimer’s disease and is increased in apolipoprotein E4 carriers

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Rosemary J Jackson ◽  
Jamie Rose ◽  
Jane Tulloch ◽  
Chris Henstridge ◽  
Colin Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Data Link ◽  
Increased Risk ◽  
Synapse Degeneration ◽  
Models Of Disease

Abstract One of the major challenges in developing effective therapeutic strategies for Alzheimer’s disease is understanding how genetic risk factors contribute to neurodegeneration. The apolipoprotein epsilon 4 isoform (APOE4) and variants in the Clusterin (CLU) gene (also known as apolipoprotein J) are associated with increased risk of developing Alzheimer’s. Our previous work demonstrated that APOE4 exacerbates synapse degeneration and synaptic accumulation of toxic oligomeric amyloid beta in human Alzheimer’s and mouse models of disease. Here, we observe clusterin in synapses in human Alzheimer's disease brain. The percentage of synapses containing clusterin is higher in APOE4 carriers than APOE3 carriers. Furthermore, we observe oligomeric amyloid beta accumulation within synapses containing clusterin which is also higher in APOE4 carriers. These data link two genetic risk factors with synapse degeneration in Alzheimer’s and support a potential role for clusterin working with APOE in causing synaptic damage.

scholarly journals Loneliness and Risk of Dementia

2018 ◽  
Vol 75 (7) ◽  
pp. 1414-1422 ◽  
Author(s):  
Angelina R Sutin ◽  
Yannick Stephan ◽  
Martina Luchetti ◽  
Antonio Terracciano
Keyword(s):  
Risk Factors ◽  
Social Isolation ◽  
Genetic Risk ◽  
Proportional Hazards ◽  
Genetic Risk Factors ◽  
Cognitive Status ◽  
Cox Proportional Hazards ◽  
Dementia Risk ◽  
Increased Risk ◽  
Modifiable Factor

Abstract Objective The present study tests whether loneliness is associated with risk of dementia in the largest sample to date and further examines whether the association is independent of social isolation, a related but independent component of social integration, and whether it varies by demographic factors and genetic vulnerability. Method Participants from the Health and Retirement Study (N = 12,030) reported on their loneliness, social isolation, and had information on clinical, behavioral, and genetic risk factors. Cognitive status was assessed at baseline and every 2 years over a 10-year follow-up with the modified Telephone Interview for Cognitive Status (TICSm). A TICSm score of 6 or less was indicative of dementia. Results Cox proportional hazards regression indicated that loneliness was associated with a 40% increased risk of dementia. This association held controlling for social isolation, and clinical, behavioral, and genetic risk factors. The association was similar across gender, race, ethnicity, education, and genetic risk. Discussion Loneliness is associated with increased risk of dementia. It is one modifiable factor that can be intervened on to reduce dementia risk.

scholarly journals Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease

2020 ◽  
Vol 4 (9) ◽  
pp. 1978-1986 ◽  
Author(s):  
Andrew Srisuwananukorn ◽  
Rasha Raslan ◽  
Xu Zhang ◽  
Binal N. Shah ◽  
Jin Han ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Genetic Risk ◽  
Clinical Laboratory ◽  
Genetic Risk Factors ◽  
Cell Disease ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Thrombotic Complications

Abstract Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.

scholarly journals Higher Native Peruvian ancestry proportion is associated with tuberculosis progression risk

2020 ◽  
Author(s):  
Samira Asgari ◽  
Yang Luo ◽  
Kamil Slowikowski ◽  
Chuan-Chin Huang ◽  
Roger Calderon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Public Health Problem ◽  
Genetic Risk Factors ◽  
Indigenous Populations ◽  
Major Public Health Problem ◽  
Road Map ◽  
Increased Risk ◽  
Latently Infected ◽  
Progression Risk

The global burden of pulmonary tuberculosis (TB) remains a major public health problem that is particularly severe among and disproportionately affects indigenous populations. We aimed to investigate whether genetic factors related to indigeneity affect TB progression risk in a cohort of admixed Peruvians with active TB and their latently infected household contacts. Our results show that Native Peruvian ancestry is positively associated with TB progression risk: a 10% increase in native ancestry tracks with a 25% increased risk of TB progression. This risk is independent of the potentially confounding socio-demographic and environmental factors that we tested here. Our results demonstrate that the genetic contribution to TB risk varies among populations and brings new insight to the long-standing debate on the role of genetic ancestry in susceptibility to TB. Additionally, our study highlights the value of including diverse populations in genetic studies of infectious diseases and other complex phenotypes, and provides a road map for future similar studies where it is important to account for confounding non-genetic risk factors to identify genetic risk factors.

scholarly journals The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) as Possible Risk Factors of Psoriasis Development

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 887
Author(s):  
Joanna Bartosińska ◽  
Szymon Zmorzyński ◽  
Beata Sarecka-Hujar ◽  
Dorota Raczkiewicz ◽  
Magdalena Wojcierowska-Litwin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Psoriatic Arthritis ◽  
Genetic Susceptibility ◽  
Plaque Psoriasis ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Healthy Controls ◽  
Increased Risk

Advances in genotypic technologies enable identification of possible associations between genetic variants of certain genes and increased risk of developing plaque psoriasis or psoriatic arthritis. The aim of the study was to analyze the NOTCH3 (6746T>C) (rs1044009) and PSMA6 (-8C>G) (rs1048990) polymorphisms and their role in genetic susceptibility to psoriasis. The study included 158 psoriatic patients and 100 healthy controls. The frequencies of the NOTCH3 genotypes differed between the psoriatic patients and healthy controls (p = 0.050). No differences were found in the distribution of PSMA6 genotypes and alleles between the psoriatic patients and healthy controls. The studied psoriatic patients presented a higher frequency of the CC genotype of PSMA6 compared to the healthy controls (8.8% vs. 2%, respectively). Psoriatic arthritis was more frequent among patients with the CC genotype of PSMA6 (p = 0.059). CC homozygosity of NOTCH3 was more commonly observed in the studied psoriatic patients than in the healthy controls (OR = 4.76, p= 0.032). The obtained data suggest that genetic variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) genes may play significant roles in psoriatic patients. Further studies are necessary to unequivocally determine their role as genetic risk factors of psoriasis development.

A Comprehensive Investigation on Potential Risk Factors for NSCL/P in a Rural District of Hebei Province, China

2021 ◽  
pp. 105566562110588
Author(s):  
Congna Chai ◽  
Lei Cheng ◽  
Jianjun Jiao ◽  
Juan Dang ◽  
Shubin Jin
Keyword(s):  
Risk Factors ◽  
Potential Risk ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Hebei Province ◽  
Healthy Children ◽  
Multivitamin Supplementation ◽  
Rural Districts ◽  
Increased Risk ◽  
Potential Risk Factors

Non syndromic cleft lip with or without palate (NSCL/P), one of the most common birth defects, is closely related to various risk factors. However, information regarding risk factors for NSCL/P in rural districts in China is very limited thus far. The objective of this study was designed to identify the potential risk factors for NSCL/P in rural districts. A comprehensive retrospective investigation including 435 NSCL/P patients and 402 healthy children was carried out in Hebei Province, China. Multiple logistic regression analysis and transmission disequilibrium test (TDT) were respectively used to identify non-genetic and genetic risk factors for NSCL/P, and then PLINK was used to explore the relationship between non-genetic and genetic risk factors. The results showed that maternal periconceptional exposure to pesticides and herbicides, as well as low parental education level were involved in the increased risk of NSCL/P, whereas maternal folic acid and multivitamin supplementation use during preconception period were associated with the reduced risk of NSCL/P. TDT analysis identified 2 single nucleotide polymorphisms (SNPs) (rs7078160 and rs4752028) in VAX1 and one SNP (rs17563) in BMP4 as the genetic risk factors for NSCL/P. Further analysis showed that the genetic risk factors were closely related with the negative non-genetic risk factors. Our study identified the potential risk factors for NSCL/P in rural districts, thus providing a theoretical basis for the prevention of NSCL/P occurrence.

scholarly journals The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) As Possible Risk Factors of Psoriasis Development

2021 ◽  
Author(s):  
Joanna Bartosińska ◽  
Szymon Zmorzyński ◽  
Beata Sarecka-Hujar ◽  
Dorota Raczkiewicz ◽  
Magdalena Wojcierowska-Litwin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Psoriatic Arthritis ◽  
Genetic Susceptibility ◽  
Plaque Psoriasis ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Healthy Controls ◽  
Increased Risk

Abstract Advances in genotypic technologies enable identification of possible associations between genetic variants of certain genes and increased risk of developing plaque psoriasis or psoriatic arthritis. The aim of the study was to analyze the NOTCH3 (6746T>C) (rs1044009) and PSMA6 (8C>G) (rs1048990) polymorphisms and their role in genetic susceptibility to psoriasis. The study included 158 psoriatic patients and 100 healthy controls. The frequencies of the NOTCH3 genotypes differed between the psoriatic patients and controls (p=0.050). No differences were found in the distribution of PSMA6 genotypes and alleles between the psoriatic patients and controls. The studied psoriatic patients presented a higher frequency of the CC genotype of PSMA6 compared to the healthy controls (8.8% vs 2%, respectively). Psoriatic arthritis was more frequent among patients with the CC genotype of PSMA6 (p=0.059). Simultaneous CC homozygosity of NOTCH3 and PSMA6 was significantly more commonly observed in the studied psoriatic patients than in the controls (p=0.032). The obtained data suggest that genetic variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) genes may play significant roles in psoriatic patients. Further studies are necessary to unequivocally determine their role as genetic risk factors of psoriasis development.

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