Search

Background: Billroth Ⅰ (BⅠ) reconstruction and Roux-en-Y (RY) reconstruction are both commonly performed after distal gastrectomy (DG). We conducted a retrospective study to evaluate which is the better option., Methods: Included in our study were 162 patients who, between April 2011 and October 2015, underwent DG followed by BⅠ reconstruction (n = 93) or RY reconstruction (n = 69). All patients were followed up for at least 1 year. We compared perioperative outcomes, postoperative complications, gastrointestinal (GI) symptoms, endoscopic findings, and nutritional status between the 2 groups of patients., Results: Patient characteristics did not differ between the 2 groups, with the exception of the incidence of gastric body tumors, which was significantly higher in the RY group (73.9% vs. 19.4%; p < 0.001). Operation time was significantly longer in the RY reconstruction group (p < 0.001). There was no significant between-group difference in the grades of GI dysfunction (p = 0.122).The endoscopically determined RGB (Residual food, Gastritis, Bile reflux)scores were significantly better in the RY reconstruction group than in the BI reconstruction group (p = 0.027, p < 0.001,p < 0.001,respectively).There was also no significant between-group difference in the change (1-year postoperative value/preoperative value) in body weight, body mass index, serum albumin concentration, or total cholesterol concentration (p = 0.484,p = 0.613,p = 0.760,p = 0.890, respectively)., Conclusions: RY reconstruction appears not to be advantageous over BⅠ reconstruction in terms of GI function or nutritional status 1 year after surgery. RY reconstruction does appear to be superior in terms of preventing bile reflux but takes more operation time., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population., Methods: Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment., Results: The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465)., Conclusions: These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.

Objective: To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption, and the susceptibility of stomach cancer in Chinese males., Methods: Three hundred and eighty-two stomach cancer patients and 382 healthy controls from Taixing and Changshu city of Jiangsu province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by PCR and denaturing high-performance liquid chromatography (DHPLC). Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI)., Results: (1) In no drinkers, compared with ALDH2G/G carriers, ALDH2 G/A (OR=1.67, 95%CI: 1.01-2.78) carriers showed a significantly elevated risk of developing stomach cancer. No association was found between ADH2 genotypes and risk of stomach cancer. (2) ALDH2 A allele carriers with cumulative amount of alcohol consumption≥2.5 (Kg*years) were at a higher risk of developing stomach cancer compared with those with cumulative amount of alcohol consumption<2.5 Kg (Kg*years) (OR=2.72, 95%CI:0.89-8.31) and ALDH2 G/G carriers with cumulative amount of alcohol consumption<2.5 (Kg*years) (OR=2.46, 95%CI=0.90-6.72) or≥2.5 (Kg * years) (OR=2.53, 95%CI=0.86-7.49). (3) Compared with individuals with ADH2 A/A and ALDH2 G/G genotypes, ADH2 G and ALDH2 A allele carriers were not at a high risk of developing stomach cancer, with regard to the status of alcohol consumption, and even cumulative amount of alcohol consumption≥1.5 (Kg*years) (OR=1.65, 95%CI:0.56-4.82)., Conclusion: ADH2 and ALDH2 polymorphisms and alcohol drinking may not play an important role in the development of stomach cancer in Chinese males.

To investigate the relationship between polymorphism in the 3'-untranslated region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA from peripheral blood leukocytes was obtained before therapy. TS 3'-UTR genotypes were detected by PCR-RFLP. Polymorphism in the TS 3'-UTR can be classified into three groups according to the presence or absence of a 6 bp nucleotide fragment: the -6/-6 bp, -6/+6 bp and +6/+6 bp groups. The response rate of the -6/-6 bp and -6/+6 bp groups was found to be significantly higher than the +6/+6 bp group. These results show that the presence of the TS 3'-UTR 6 bp nucleotide fragment can be correlated with the sensitivity of gastric cancer to 5-FU-based chemotherapy, and that the TS 3'-UTR polymorphism profile can be used to guide the choice of 5-FU-based chemotherapy in advanced gastric cancer.

Objective: To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC)., Methods: 75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method., Results: (1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different., Conclusion: These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.

Background & Objective: Methylenetrahydrofolate reductase (MTHFR) C677T polymorphism modifies enzyme activity and thus effects the level of 5, 10-methylenetetrahydrofolate (5,10-MTHR), which correlates with the tumor response to 5-fluorouracil (5-FU). This study was to evaluate the effect of MTHFR C677T polymorphism on chemosensitivity and toxicity to 5-FU in patients with gastric carcinoma., Methods: A total of 75 patients with histologically confirmed advanced gastric carcinoma were included. All patients received 5-fluoropyrimidine-based chemotherapy. Two milliliters of peripheral blood was extracted from each patient before treatment. PCR-RFLP was used to determine the genotypes of MTHFR, including wild-type homozygotes (C/C), heterozygotes (C/T), and mutant homozygotes (T/T)., Results: C/C genotype presented in 24 patients (24/75, 32.0%), C/T genotype presented in 33 patients (33/75, 44.0%), and T/T genotype presented in 18 patients (18/75, 24.0%). Total response rate of chemotherapy was 29.3%, among which 22 with partial response, 29 with no change, and 24 with progressive disease. Response rate in patients with T/T genotype (20/24, 83.3%) was significantly greater than either that in patients with C/C genotype (2/24, 8.3%) (Chi2=24.01, P< 0.001), or that in patients with C/T genotype (5/33, 15.2%) (Chi2=22.7, P< 0.001). There was no difference of response rate between C/C and C/T genotypes (Chi2=0.6, P=0.439). Multiple variances logistic regression analysis (adjusted for gender, age, chemotherapy regimens, and adjuvant chemotherapy factors) showed that the probability of chemotherapy work on patients with combination of C/C and C/T genotypes was 0.017-fold to that in patients with T/T genotype (95% CI ranging from 0.003 to 0.102, P< 0.001); incidence of treatment-related side effects, vomiting and nausea, was significantly greater in latter patients than in former patients (Chi2=12.264, P=0.002)., Conclusions: MTHFR C677T polymorphism can predict the effects and toxicity of 5-fluoropyrimidine-based chemotherapy in advanced gastric carcinoma.

Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.

Objective: To evaluate interactions between lifestyle, methylanetetrahydrofolate reductase gene (MTHFR) and polymorphisms in the 3'-untranslated region (3'-UTR) of the thymidylate synthase gene (TS) with reference to development of stomach cancer (SC)., Methods: We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. TS genotypes were identified by polymerase chain reaction., Results: (1) The frequencies of TS genotypes (+6 bp/+6 bp, +6 bp/-6 bp and -6 bp/-6 bp) among the cases were 5.6%, 47.7% and 46.7% and among the controls were 9.0%, 54.0% and 37.0%, respectively. Individuals identified as -6 bp/-6 bp genotype had a slightly higher risk for SC than those individuals with +6 bp alleles (the crude OR = 1.49, 95% CI: 0.90 - 2.47; adjusted OR = 1.36, 95% CI: 1.00 - 1.78, P = 0.047). (2) Individuals having TS -6 bp/-6 bp genotype and having smoking habit were at a significantly higher risk of developing SC (adjusted OR = 2.79, 95% CI: 1.51 - 5.18) compared with those who had +6 bp alleles with no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing SC (adjusted OR = 1.76, 95% CI: 1.07 - 2.90) compared with those with +6 bp alleles and low consumption of alcohol. As compared with individuals with +6 bp alleles and who had habit of tea drinking, individuals who had TS -6 bp/-6 bp genotype and but without habit of tea drinking had an increased risk of developing SC (adjusted OR = 2.34, 95% CI: 1.43 - 3.82). (3) Individuals with TS -6 bp/-6 bp genotype and with MTHFR T alleles had an increased risk of developing SC (adjusted OR = 2.67, 95% CI: 1.07 - 6.70) compared with those with +6 bp alleles and with MTHRF C/C genotype., Conclusion: Results in the present study suggested that there was a combined effect between lifestyle, MTHFR C/T or T/T genotype and TS -6 bp/-6 bp genotype in the development of SC.

To evaluate interactions between lifestyle factors and glutathione-S-transferases M1 (GSTM1) and GSTT1 genotypes with reference to development of esophageal and stomach cancers, we conducted a case-control study of 141 cases of esophageal cancer, 153 cases of stomach cancer and 223 population-based controls in Huaian City of Jiangsu Province, China. GSTM1 and GSTT1 genotypes were identified by multiplex polymerase chain reaction. The GSTM1 null genotype was associated with an increased odds ratio for esophageal cancer (2.17, 95% confidence interval=1.35-3.50), but not for stomach cancer. A combined effect was also observed between smoking and the GSTM1 null genotype with regard to esophageal risk. Tea drinking was a protective factor for both cancers, its effect being independent of the GSTT1 and GSTM1 genotypes. These findings suggest the GSTM1 polymorphism is involved in the susceptibility to esophageal cancer development, and tea consumption reduces the risk of esophageal and stomach cancers.

Oxidative stress is involved in many types of DNA damage, e.g., resulting in 8-hydroxyguanine adducts. Since a human counterpart exists for the yeast gene OGG1 (hOGG1) encoding an enzyme that repairs 8-hydroxyguanine, its polymorphism, Ser(326)Cys, might have potential as a genetic marker for cancer susceptibility. To investigate its association with stomach cancer risk and possible interactions with environmental factors, we conducted a case-control study of 101 stomach cancer cases and 198 controls using PCR-single-strand conformation polymorphism and a questionnaire approach. The proportional distribution of the Cys/Cys alleles did not differ between stomach cancer cases and controls, but subgroup analyses revealed that a frequent drinking habit elevated the odds ratio (OR) for stomach cancer in Cys/Cys compared to Ser/Ser and Ser/Cys carriers. The ORs with frequent consumption of pickled vegetables and meat tended to be higher in Cys/Cys than in Ser/Ser and Ser/Cys carriers, these interactions being on the borderline of statistical significance. Our findings suggest that the hOGG1 Ser(326)Cys polymorphism may alter the impact of some environmental factors on stomach cancer development. For confirmation, an additional study with a larger number of subjects is now required., (Copyright 2002 Wiley-Liss, Inc.)