scholarly journals Interaction ofXRCC1Arg399Gln Polymorphism and Alcohol Consumption Influences Susceptibility of Esophageal Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Man Li ◽  
Xia Yu ◽  
Zhi-yan Zhang ◽  
Chun-long Wu ◽  
Hai-long Xu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Alcohol Consumption ◽  
Potential Interaction ◽  
Han Chinese ◽  
Healthy Controls ◽  
Wild Type ◽  
Pcr Rflp ◽  
Chinese Descent ◽  
Arg399gln Polymorphism

Background. To explore the correlation between the Arg399Gln polymorphism and susceptibility to esophageal cancer in Korean and Han Chinese individuals in Harbin, China, and its potential interaction with alcohol consumption.Methods. This prospective study included 203 patients with esophageal squamous cell carcinoma; 88 were of Korean descent and 115 were of Han Chinese descent. A group of healthy controls included 105 participants of Korean descent and 105 of Han Chinese descent. Genotyping of the Arg399Gln locus ofXRCC1was performed by PCR-RFLP.Results. The allelic and genotypic frequencies were not significantly different between individuals with esophageal cancer and controls or between individuals of Korean and Han Chinese descent (P>0.05). However, when individuals with the wild-type Arg/Arg genotype also consumed alcohol, the risk of esophageal cancer was lower (OR = 3.539; 95% CI = 2.039–6.142;P<0.05).Conclusions. TheXRCC1Arg399Gln polymorphism does not appear to be associated with esophageal cancer in individuals of Korean or Han Chinese descent in Harbin, China. However, alcohol consumption may decrease the risk of esophageal cancer in persons with the wild-type genotype.

scholarly journals Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hind Hassani Idrissi ◽  
Wiam Hmimech ◽  
Nada El Khorb ◽  
Hafid Akoudad ◽  
Rachida Habbal ◽  
...  
Keyword(s):  
Acute Coronary Syndromes ◽  
Interindividual Variability ◽  
Potential Effect ◽  
Healthy Controls ◽  
Wild Type ◽  
Pcr Rflp ◽  
Verifynow Assay ◽  
Coronary Syndromes ◽  
Development Risk ◽  
Transmission Models

Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (−) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (−) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58–5.05], P=0.01 and OR [95% CI] = 1.23 [0.74–2.03], P<0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development.

scholarly journals Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shunsuke Shiba ◽  
Nobuhiro Nakamoto ◽  
Po-Sung Chu ◽  
Keisuke Ojiro ◽  
Nobuhito Taniki ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Transgenic Mice ◽  
Inflammatory Cytokines ◽  
Gene Polymorphisms ◽  
Healthy Controls ◽  
Wild Type ◽  
Excessive Alcohol Consumption ◽  
Alcohol Abstinence ◽  
Excessive Alcohol ◽  
Alcohol Dependent

AbstractIncreased intestinal permeability and hepatic macrophage activation by endotoxins are involved in alcohol-induced liver injury pathogenesis. Long-term alcohol exposure conversely induces endotoxin immune tolerance; however, the precise mechanism and reversibility are unclear. Seventy-two alcohol-dependent patients with alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) gene polymorphisms admitted for alcohol abstinence were enrolled. Blood and fecal samples were collected on admission and 4 weeks after alcohol cessation and were sequentially analyzed. Wild-type and ALDH2*2 transgenic mice were used to examine the effect of acetaldehyde exposure on liver immune responses. The productivity of inflammatory cytokines of peripheral CD14+ monocytes in response to LPS stimulation was significantly suppressed in alcohol dependent patients on admission relative to that in healthy controls, which was partially restored by alcohol abstinence with little impact on the gut microbiota composition. Notably, immune suppression was associated with ALDH2/ADH1B gene polymorphisms, and patients with a combination of ALDH2*1/*2 and ADH1B*2 genotypes, the most acetaldehyde-exposed group, demonstrated a deeply suppressed phenotype, suggesting a direct role of acetaldehyde. In vitro LPS and malondialdehyde-acetaldehyde adducted protein stimulation induced direct cytotoxicity on monocytes derived from healthy controls, and a second LPS stimulation suppressed the inflammatory cytokines production. Consistently, hepatic macrophages of ethanol-administered ALDH2*2 transgenic mice exhibited suppressed inflammatory cytokines production in response to LPS compared to that in wild-type mice, reinforcing the contribution of acetaldehyde to liver macrophage function. These results collectively provide new perspectives on the systemic influence of excessive alcohol consumption based on alcohol-metabolizing enzyme genetic polymorphisms.

Relationship of oral acetaldehyde concentration and oral microflora with the development of superficial pharyngeal or esophageal squamous cell carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 57-57
Author(s):  
Toshiro Iizuka ◽  
Daisuke Kikuchi ◽  
Shu Hoteya ◽  
Mamoru Tanaka ◽  
Mitsuru Kaise
Keyword(s):  
Cluster Analysis ◽  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Alcohol Consumption ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Odds Ratio ◽  
Multivariable Analysis ◽  
Oral Microflora ◽  
Acetaldehyde Concentration

57 Background: Acetaldehyde in alcoholic beverages is evidently carcinogenic to the pharynx and esophagus. The relationship between microflora in the gastrointestinal tract and carcinogenesis, such as that between Helicobacter pyloriand gastric cancer, has attracted attention; however, there are few reports of oral microflora influencing the developing the squamous cell carcinoma of the pharynx or esophagus. Therefore, we investigated factors that might influence the development of cancer in the pharynx and esophagus. Methods: A total of 82 patients participated in this study and consisted of 50 with pharyngeal or esophageal cancer treated by endoscopic submucosal dissection and 32 with no cancer. Chromosomal DNA was extracted from bacteria in the oral mucosa, and terminal restriction fragment length polymorphism analysis was carried out. The concentration of acetaldehyde in saliva was measured, and clinical factors were assessed by multivariable analysis. Results: The average values of clinical parameters in patients with pharyngeal or esophageal cancer were as follows: age, 68 years; acetaldehyde, 2.5 μmol/l; GOT, 30.5 IU/l; GPT, 23.5 IU/l; γGTP, 79.4 IU/l; Hb, 14.1 g/dl; MCV, 97.6 fl; alcohol consumption, 6.1 g/day; and Brinkman index, 764. In patients with no cancer, the same parameters were as follows: age, 69 years; acetaldehyde, 4.8 μmol/l; GOT, 23 IU/l; GPT, 21.9 IU/l; γGTP, 36.9 IU/l; Hb, 14.2 g/dl; MCV, 93.7 fl; alcohol consumption, 1.9 g/day, and Brinkman index, 350. Multivariable analysis showed that acetaldehyde concentration (odds ratio: 0.63; 95% CI: 0.47–0.85) and alcohol consumption (odds ratio: 1.64; 95% CI: 1.19–2.25) were significantly different between the two groups. Cluster analysis extracted 16 small clusters from the dendrogram. In 3 clusters among them, the percentage of patients with cancer was more than 80%. Conclusions: Cluster analysis revealed three clusters with a high incidence of cancer patients. Therefore, acetaldehyde concentration and alcohol consumption may be related with carcinogenesis of the pharynx and esophagus. We intend to identify the microbial flora of each cluster in a future study.

Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

2019 ◽  
Vol 19 (3) ◽  
pp. 206-215
Author(s):  
HariOm Singh ◽  
Nayana Nambiar ◽  
Dharmesh Samani ◽  
Raman R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Interleukin 2 ◽  
Promoter Polymorphism ◽  
Healthy Controls ◽  
Hiv Replication ◽  
Hiv Patients ◽  
Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

scholarly journals Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma

2006 ◽  
Vol 119 (7) ◽  
pp. 1717-1722 ◽  
Author(s):  
Antonio Rosato ◽  
Michela Pivetta ◽  
Anna Parenti ◽  
Gaetano A. Iaderosa ◽  
Alessia Zoso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Squamous Cell

scholarly journals Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keping Chen ◽  
Peng Xiao ◽  
Guochun Li ◽  
Chunling Wang ◽  
Chuankun Yang
Keyword(s):  
Genetic Polymorphisms ◽  
Venous Blood ◽  
Gene Chip ◽  
Han Chinese ◽  
Genotype Frequency ◽  
Wild Type ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Patients ◽  
Genotype Frequencies ◽  
Combined Genotypes

Abstract Background There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. Methods Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. Results The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. Conclusions These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

scholarly journals Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhiyong Wang ◽  
Yusuke Goto ◽  
Michael M. Allevato ◽  
Victoria H. Wu ◽  
Robert Saddawi-Konefka ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck ◽  
Mtor Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Mtor Signaling ◽  
Wild Type ◽  
Oncogenic Signaling ◽  
Signaling Axis ◽  
Oncogenic Driver ◽  
Cancer Remission

AbstractImmune checkpoint blockade (ICB) therapy has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment, but <20% of patients achieve durable responses. Persistent activation of the PI3K/AKT/mTOR signaling circuitry represents a key oncogenic driver in HNSCC; however, the potential immunosuppressive effects of PI3K/AKT/mTOR inhibitors may limit the benefit of their combination with ICB. Here we employ an unbiased kinome-wide siRNA screen to reveal that HER3, is essential for the proliferation of most HNSCC cells that do not harbor PIK3CA mutations. Indeed, we find that persistent tyrosine phosphorylation of HER3 and PI3K recruitment underlies aberrant PI3K/AKT/mTOR signaling in PIK3CA wild type HNSCCs. Remarkably, antibody-mediated HER3 blockade exerts a potent anti-tumor effect by suppressing HER3-PI3K-AKT-mTOR oncogenic signaling and concomitantly reversing the immune suppressive tumor microenvironment. Ultimately, we show that HER3 inhibition and PD-1 blockade may provide a multimodal precision immunotherapeutic approach for PIK3CA wild type HNSCC, aimed at achieving durable cancer remission.

scholarly journals Whole exome sequencing and deep sequencing of esophageal squamous cell carcinoma and adenocarcinoma in Japanese patients using the Japanese version of the Genome Atlas, JCGA

Esophagus ◽  
2021 ◽  
Author(s):  
Eisuke Booka ◽  
Yasuhiro Tsubosa ◽  
Tomoya Yokota ◽  
Shuhei Mayanagi ◽  
Kenjiro Ishii ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Somatic Mutations ◽  
Molecular Targets ◽  
Japanese Version ◽  
Japanese Patients ◽  
Genetic Alterations ◽  
Genome Atlas

Abstract Background Recent comprehensive mutation analyses have revealed a relatively small number of driver mutations in esophageal cancer, implicating a limited number of molecular targets, most of which are also implicated in squamous cell carcinoma. Methods In this study, we investigated genetic alterations in 44 esophageal squamous cell carcinomas (ESCC) and 8 adenocarcinomas (EAC) from Japanese patients as potential molecular targets, based on data from the Japanese version of The Genome Atlas (JCGA). Results Esophageal cancer was characterized by TP53 somatic mutations in ESCC (39/44, 88.6%) and EAC (5/8, 62.5%). In addition to TP53 mutations, somatic mutations in NFE2L2 (16/44, 36.4%), CDKN2A (7/44, 15.9%), and KMT2D (7/44, 15.9%) were more frequently detected in ESCC than in EAC. WRN-truncated type mutations that lead to genomic instability correlate with EAC, but not ESCC. ESCC samples were enriched in ALDH2-associated mutational signature 16 as well as the APOBEC signature. Patients with FAT2 mutations had significantly poorer overall survival compared with those with wild-type status at FAT2 (p < 0.05). Patients with EP300 or PTPRD mutations also had poor progression-free survival compared with respective wild-types (p < 0.05 or p < 0.001). Conclusions These findings may facilitate future precision medicine approaches based on genomic profiling in ESCC and EAC.

scholarly journals PCR-based genotyping assays to detect germline APC variant associated with hereditary gastrointestinal polyposis in Jack Russell terriers

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kyoko Yoshizaki ◽  
Akihiro Hirata ◽  
Hiroyuki Matsushita ◽  
Naohito Nishii ◽  
Mifumi Kawabe ◽  
...  
Keyword(s):  
Mutant Allele ◽  
False Negative ◽  
Disease Onset ◽  
Pcr Amplification ◽  
Buccal Swab ◽  
Wild Type ◽  
Gastrointestinal Polyposis ◽  
Pcr Rflp ◽  
Formalin Fixed Paraffin Embedded ◽  
Rflp Assay

Abstract Background The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs. Result First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays. Conclusion In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.

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