Thymidylate synthase genetic polymorphisms and cancer risk: a meta-analysis of 37 case-control studies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies have evaluated the association between polymorphisms of thymidylate synthase (TS) and cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to evaluate the association using a meta-analysis.</p><p><b>METHODS</b>A comprehensive search was conducted to identify all case-control studies on TS on a 28-bp tandem repeats in 5'untranslated region (5'UTR) and a 6-bp insertion (ins) and deletion (del) mutation in 3'UTR of the gene and cancer risk. Meta-analysis was conducted using a fixed and random effect model.</p><p><b>RESULTS</b>Our meta-analysis on a total of 13 307 cancer cases and 18 226 control subjects from 37 published case-control studies showed no significant association between the risk of cancer and the 5'UTR 28-bp tandem repeats polymorphism (3R/3R vs. 2R/2R: OR = 1.06, 95%CI, 0.93 - 1.20) or the 3'UTR 6-bp ins/del polymorphism (del6/del6 vs. ins6/ins6: OR = 0.93, 95%CI, 0.81 - 1.08) with significant between-study heterogeneity. In the cancer type- and ethnic subgroup-stratification analyses, we did not find any association between TS polymorphisms and cancer risk either.</p><p><b>CONCLUSION</b>TS 5'UTR 28-bp tandem repeats and 3'UTR 6-bp ins/del polymorphisms may not be associated with cancer risk.</p>

Inhibition of the proliferation and invasion of pancreatic cancer cells by MAT1 gene-targeted short interfering RNA in vitro / 肿瘤

Objective: To observe the influence of silencing MAT1 gene by short interfering RNA (siRNA) on the proliferation and invasion of human pancreatic cancer cells and discuss the feasibility of using MAT1 gene as therapeutic target for treatment of pancreatic cancer. Methods: BxPC-3 cells were transfected with sequence-specific siRNA targeting MAT1 gene with liposome mediation. The mRNA and protein expression of MAT1 were confirmed by RT-PCR and Western blot, respectively. The cell proliferation was measured by Trypan blue exclusion staining. The invasion ability was determined by Boyden chamber model in vitro. Results: The mRNA and protein expression of MAT1 were significantly down-regulated by siRNA in BxPC-3 cells compared with the control groups. The expression of MAT1 mRNA was reduced by 55.2% and 64.3% at 24 h and 48 h, respectively (P <0.01). The cell proliferation and invasion ability of BxPC-3 cells were significantly inhibited in vitro (P < 0.01). Conclusion: The results suggest that siRNA targeting MAT1 gene inhibits the cell proliferation and invasion of BxPC-3 cells in vitro. MAT1 may be a potential target for gene therapy of human pancreatic cancer.