SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients / 癌症

<p><b>BACKGROUND</b>Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship.</p><p><b>METHODS</b>The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association.</p><p><b>RESULTS</b>Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01-1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00-1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00-1.21).</p><p><b>CONCLUSION</b>SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.</p>

Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

Relationship between polymorphisms of related genes in the folic acid metabolic pathway and the survival of gastric cancer patients treated with capecitabine combined with paclitaxel / 肿瘤

Objective: To investigate the association of polymorphisms of related genes in folic acid metabolic pathway and the tumor candidate genes with the survival of gastric cancer patients treated with capecitabine combined with paclitaxel. Methods: Ninety-three patients with pathological diagnosis of gastric cancer were treated with capecitabine plus paclitaxel-based chemotherapy. The gene polymorphisms of tumor necrosis factor ( TNF) A308G (rs1800629), methylenetetrahydrofolate reductase ( MTHFR) C677T (rs1801131) and A1298C (rs1801133), methionine synthase ( MTR) A2756G (rs1805087) and methionine synthase reductase ( MTRR) A66G (rs1801394) were detected by TaqMan-MGB probe typing method. The median survival time (MST) of patients with different genotypes was compared, and the effects of various factors on the prognosis were evaluated. Results: The median follow-up period was 29.6 months. The MST of 93 patients was 34.93 months. The MST of patients with MTHFR 1298CA and 1298CC were 47.50 and 22.91 months, respectively. The log-rank test revealed that the polymorphism of MTHFR 1298C/A had marginally significant correlation with the survival of patients (χ2=3.447, P=0.062), and other gene polymorphisms were not associated with the survivals. The gender, drinking and operation were the major prognostic factors for gastric cancer patients receiving chemotherapy. Conclusion: Detection of MTHFR 1298CA polymorphism may predict the survival of gastric cancer patients receiving chemotherapy of capecitabine combined with paclitaxel.

Oxaliplatin Induced Neurotoxicity: Characteristic and Therapy / 上海第二医科大学学报

Oxaliplatin, the third generation of the platinum based chemotherapy agent, is effective in the treatment of multiple solid tumors and is also quite safe. However, there is a high incidence of peripheral neurotoxiciy, which is dose-limiting. Oxaliplatin induces two distinct forms of neurotoxicity: an acute syndrome that is triggered or aggravated by exposure to cold, and chronic cumulative sensory neurotoxicity which in nature resembles characteristics of cisplatin associated neurotoxicity. In this article, the clinical manifestations, electrophysiologic abnormalities, mechanism of neurotoxicity and therapy are reviewed.

Association between functional genetic polymorphisms of IL-1B and IL-1RN and susceptibility to gastric cancers / 上海第二医科大学学报

Objective To study the association between functional genetic polymorphisms of IL-1B(T-31C,C-511T),IL-1RN and the susceptibility to gastric cancers. Methods A case-control study was conducted in 180 gastric cancer cases and 308 age-and sex-matched cancer-free controls.Genotypes were detected by PCR-restriction fragment length polymorphism(PCR-RFLP) assays,and association between genotypes,environmental factors and risk of gastric cancers were determined. Results IL-1B T-31C was in strong linkage disequilibrium with IL-1B C-511T(D'=0.862,R2= 0.721,P=0.000).Multivariate logistic regression analysis revealed that the variant genotypes of IL-1B T-31C and C-511T were not significantly associated with risks for gastric cancers(adjusted OR,0.95 and 95% CI,0.62-1.47 for IL-1B T-31C;and adjusted OR,0.85 and 95% CI,0.55-1.31 for IL-1B C-511T).The variant genotypes(1/2,2/2) in IL-1RN were associated with a non-significantly increased risks for gastric cancers(adjusted OR,1.32 and 95% CI,0.71-2.36) in all subjects and with a significantly increased risks for gastric cancers in subjects with H.pylori infection(adjusted OR,2.03 and 95%CI,1.02-4.80).Conclusion The functional genetic polymorphisms of IL-1RN may contribute to the risks of gastric cancers in high-risk population,particularly in those with H.pylori infection.