27 research outputs found

    Association of a Deletion of GSTT2B with an Altered Risk of Oesophageal Squamous Cell Carcinoma in a South African Population: A Case-Control Study

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    Polymorphisms in the Glutathione S-transferase genes are associated with altered risks in many cancers, but their role in oesophageal cancer is unclear. Recently a 37-kb deletion polymorphism of GSTT2B that reduces expression of GSTT2 has been described. We evaluated the influence of the GSTT1 and GSTT2B deletion polymorphisms, and the GSTP1 Ile105Val polymorphism (rs1695) on susceptibility to oesophageal squamous cell carcinoma (OSCC) in the Black and Mixed Ancestry populations of South Africa.The GSTT1, GSTT2B and GSTP1 variants were genotyped in 562 OSCC cases and 907 controls, and tested for association with OSCC and for interaction with smoking and alcohol consumption. Linkage disequilibrium (LD) between the deletions at GSTT1 and GSTT2B was determined, and the haplotypes tested for association with OSCC. Neither the GSTT1 deletion nor the GSTP1 Ile105Val polymorphism was associated with OSCC risk in the Black or Mixed Ancestry populations. The GSTT2B deletion was not associated with OSCC risk in the Black population, but was associated with reduced risk of OSCC in the Mixed Ancestry population (OR=0.71; 95% CI 0.57-0.90, p=0.004). Case-only analysis showed no interaction between the GST polymorphisms and smoking or alcohol consumption. LD between the neighboring GSTT1 and GSTT2B deletions was low in both populations (r(2)(Black)=0.04; r(2)(MxA)=0.07), thus these deletions should be assessed independently for effects on disease risk.Although there was no association between the GSTT1 deletion polymorphism or the GSTP1 Ile105Val polymorphism with OSCC, our results suggest that the presence of the recently described GSTT2B deletion may have a protective effect on the risk of OSCC in the Mixed Ancestry South African population. This is the first report of the contribution of the GSTT2B deletion to cancer risk

    Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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    Peer reviewe

    Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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    Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

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    Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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    QTL mapping for brown rot (Monilinia fructigena) resistance in an intraspecific peach (Prunus persica L. Batsch) F1 progeny

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    Brown rot (BR) caused by Monilinia spp. leads to significant post-harvest losses in stone fruit production, especially peach. Previous genetic analyses in peach progenies suggested that BR resistance segregates as a quantitative trait. In order to uncover genomic regions associated with this trait and identify molecular markers for assisted selection (MAS) in peach, an F1 progeny from the cross "Contender" (C, resistant) 7 "Elegant Lady" (EL, susceptible) was chosen for quantitative trait loci (QTL) analysis. Over two phenotyping seasons, skin (SK) and flesh (FL) artificial infections were performed on fruits using a Monilinia fructigena isolate. For each treatment, infection frequency (if) and average rot diameter (rd) were scored. Significant seasonal and intertrait correlations were found. Maturity date (MD) was significantly correlated with disease impact. Sixty-three simple sequence repeats (SSRs) plus 26 single-nucleotide polymorphism (SNP) markers were used to genotype the C 7 EL population and to construct a linkage map. C 7 EL map included the eight Prunus linkage groups (LG), spanning 572.92 cM, with an average interval distance of 6.9 cM, covering 78.73 % of the peach genome (V1.0). Multiple QTL mapping analysis including MD trait as covariate uncovered three genomic regions associated with BR resistance in the two phenotyping seasons: one containing QTLs for SK resistance traits near M1a (LG C 7 EL-2, R2 = 13.1-31.5 %) and EPPISF032 (LG C 7 EL-4, R2 = 11-14 %) and the others containing QTLs for FL resistance, near markers SNP_IGA_320761 and SNP_IGA_321601 (LG3, R2 = 3.0-11.0 %). These results suggest that in the C 7 EL F1 progeny, skin resistance to fungal penetration and flesh resistance to rot spread are distinguishable mechanisms constituting BR resistance trait, associated with different genomic regions. Discovered QTLs and their associated markers could assist selection of new cultivars with enhanced resistance to Monilinia spp. in fruit

    No role for glutathione S-transferase genotypes in Caucasian esophageal squamous cell or adenocarcinoma etiology: an European case-control study

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    Contains fulltext : 118871.pdf (publisher's version ) (Open Access)BACKGROUND: Identifying and monitoring high-risk patients can aid the prevention of esophageal cancer (EC). The interaction of environmental risk factor exposure and genetic susceptibility may contribute to the etiology of EC. Biotransformation enzymes such as Glutathione S-Transferases (GSTs ) detoxify mutagenic and genotoxic compounds and therefore control the rate of detoxification of carcinogens. Functional polymorphisms in the genes coding for GSTs alter their enzyme activity in vitro, and were reported to modify EC risk in Asians. We hypothesized that altered enzyme activity GST genotypes influence the susceptibility for esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) in Caucasians. METHODS: We performed a case-control study including 440 Caucasian patients with EC and 592 healthy Caucasian controls matched for age and sex. Functional polymorphisms were selected and genotypes were determined in GST classes Alpha, Mu, Theta and Pi by means of polymerase chain reaction. Genotypes were classified into predicted high, intermediate and low enzyme activity categories based on in vitro activity data. The distribution of the activity genotypes were compared between patients with EAC or ESCC, and controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analyses. Gene-gene interactions were tested and for comparison purposes, the predicted low and intermediate activity genotypes were combined. Genotypes with similar risks for EAC or ESCC were combined and analyzed for multiplicative effects. RESULTS: Our analyses includes 327 patients with EAC and 106 patients with ESCC. Low or intermediate activity enzyme genotypes for GSTM1, GSTA1, GSTP1 I105V and A114V as well as for GSTT1, did not significantly modify the risk for ESCC or EAC in our Dutch population. CONCLUSION: Functional genotypes in GST genes are not involved in EAC or ESCC susceptibility in Caucasians, in contrast to results on ESCC from Asia or Africa

    Polymorphisms in alcohol-metabolizing enzymes and esophageal carcinoma susceptibility: a Dutch Caucasian case-control study

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    Contains fulltext : 125778.pdf (publisher's version ) (Closed access)Esophageal cancer (EC), mainly consisting of squamous cell carcinoma (ESCC) in the Eastern world and adenocarcinoma (EAC) in the Western world, is strongly associated with dietary factors such as alcohol use. We aimed to clarify the modifying role in EC etiology in Caucasians of functional genotypes in alcohol-metabolizing enzymes. In all, 351 Caucasian patients with EC and 430 matched controls were included and polymorphisms in CYP2E1, ADH and near ALDH2 genes were determined. In contrast to the results on ESCC in mainly Asian studies, we found that functional genotypes of alcohol-metabolizing enzymes were not significantly associated with EAC or ESCC in an European population
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