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Characterization and strong risk association of TLR2 del-196 to-174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第5期12卷 535-548页

作者： Caroline de Matos Lourenco Manoela Dias Susi Mariah Cristina Antunes do Nascimento Vilson Serafim Junior Ana Paula Simedan Vila gabriela helena rodrigues-flemming Eny Maria Goloni-Bertollo Ana Elizabete Silva Juliana Garcia de Oliveira-Cucolo Department of Graduate-Level Research Sacred Heart UniversityBauruSao Paulo 17011-970Brazil Department of Molecular Biology Sao Josédo Rio Preto School of MedicineSao Josédo Rio PretoSao Paulo 15090-000Brazil Department of Biology Sao Paulo State UniversitySao Josédo Rio PretoSao Paulo 15054-000Brazil

BACKGROUND Toll-like receptor-2(TLR2) is responsible for recognizing Helicobacter pylori(***) and activating the immune response. Polymorphisms in TLR2 may modulate gastric *** To evaluate whether the TLR2 19216 T/C(rs3804099) and TLR2-196 to-174 ins/del(rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA *** DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples[202 gastric cancer(GC), 269 chronic gastritis(CG), and 383 control/healthy(C)]and genotyped by allele-specific PCR or restriction fragment length polymorphism(RFLP)-PCR. Quantitative polymerase chain reaction by Taq Man■ assay was used to quantify TLR2 mRNA levels in fresh gastric tissues(48 GC, 36 CG, and 14 C).RESULTS Regarding the TLR2-196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models(codominant, dominant, recessive, overdominant and log-additive;P < 0.0001). Similarly, an increased risk was observed when comparing the GC and CG groups [codominant(P < 0.0001), dominant(P <0.0001), recessive(P = 0.0260), overdominant(P < 0.0001) and log-additive(P <0.0001)]. In contrast, TLR2 19216 T/C was associated with a protective effect in the GC group compared to the C group [dominant(P = 0.0420) and log-additive(P =0.0300)]. Regarding the association of polymorphisms with H. pylori infection,individuals infected with H. pylori and harboring the TLR2-196 to-174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant(P =0.0120), dominant(P = 0.0051), overdominant(P = 0.0240) and log-additive(P =0.0030)], while TLR2 19216 T/C was associated with a protective effect[codominant(P = 0.0039), dominant(P < 0.0001), overdominant(P = 0.0097) and log-additive(P = 0.0021)]. TLR2 mRNA levels were sig

关键词： Toll-like receptor 2 Helicobacter pylori Gastric cancer Chronic gastritis Polymorphisms Gene expression

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Molecular evaluation of glutathione S transferase family genes in patients with sporadic colorectal cancer

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World Journal of Gastroenterology 2018年第39期24卷 4462-4471页

作者： gabriela helena rodrigues-Fleming Glaucia Maria de Mendonca Fernandes Anelise Russo Patrícia Matos Biselli-Chicote Joao Gomes Netinho Erika Cristina Pavarino Eny Maria Goloni-Bertollo Genetics and Molecular Biology Research Unit-UPGEM Sao Jose do Rio Preto Medical SchoolFAMERPSao Jose do Rio PretoSP 15090-000Brazil Department of Surgery and Coloproctology Sao Joes do Rio Preto Medical SchoolFAMERPSao Joes do Rio PretoSP 15090-000Brazil

AIM To evaluate the association between polymorphismsin glutathione S transferases(GSTs) and the risk of sporadic colorectal cancer(SCRC), tumor progression and the survival of *** A case-control study of 970 individuals from the Brazilian population was conducted(232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension(T), affected lymph nodes(N), and presence of metastasis(M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio(OR) and 95% confidence interval(CI). The level of significance was set at 5%(P ≤ 0.05).RESULTS Age equal to or over 62 years(OR = 8.79; 95%CI: 5.90-13.09, P < 0.01) and female gender(OR = 2.91; 95%CI: 1.74-4.37; P < 0.01) were associated with increased risk of SCRC. Analysis of the polymorphisms revealed an association between the GSTM1 polymorphisms and a risk of SCRC(OR = 1.45; 95%CI: 1.06-2.00; P = 0.02), as well as between GSTT1 and a reduced risk of the disease(OR = 0.65; 95%CI: 0.43-0.98; P = 0.04). An interaction between the presence of the wild-type allele of GSTP1 Ile105 Val polymorphism and tobacco consumption on risk of SCRC(OR = 2.33; 95%CI: 1.34-4.05; P = 0.05) was observed. There was an association between the GSTM1 null genotype and the presence of advanced tumors(OR = 2.33; 95%CI: 1.23-4.41; P = 0.009), as well as increased risk of SCRC in the presence of a combination of GSTT1 non-null/GSTM1 null genotypes(OR = 1.50; 95%CI: 1.03-2.19; P = 0.03) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 1.85; 95%CI: 1.01-3.36, P = 0.04). Combined GSTT1 non-null/GSTM1 null genotypes(OR = 2.40; 95%CI: 1.19-4.85; P = 0.01) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 2.92; 95%CI: 1.05-8.12; P

关键词： Colorectal neoplasms Smoking Alcohol Glutathione S transferase Genetic polymorphisms

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CYP1A1,CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

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World Journal of Gastroenterology 2016年第45期22卷 9974-9983页

作者： Glaucia Maria M Fernandes Anelise Russo Marcela Alcantara Proenca Nathalia Fernanda Gazola gabriela helena rodrigues Patrícia Matos Biselli-Chicote Ana Elizabete Silva Joao Gomes Netinho érika Cristina Pavarino Eny Maria Goloni-Bertollo Genetics and Molecular Biology Research Unit-UPGEM Department of Molecular Biology Sao José do Rio Preto Medical School FAMERP Departament of Biology UNESP-Sao Paulo State University Departament of Surgery and Coloproctology Service Sao José do Rio Preto Medical School FAMERP

AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version *** Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P < 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with *** In conclusion, the

关键词： Single-nucleotide polymorphisms Colorectal neoplasms Cytochrome P-450 CYP2E1 Cytochrome P-450 CYP1A1 Epoxide hydrolases 1

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