Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are ...Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.展开更多
Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of pati...Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.展开更多
文摘Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.
基金funded by the Associazione Giacomo Onlus 2012-2020(Castiglioncello,Italy)(to Mini E)Fondazione Cassa di Risparmio di Firenze-ref.no.2013.0842 and ref.no.2014.0969(Firenze,Italy)(to Nobili S).
文摘Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.
