[Objective] To investigate the association between -31C/G polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer in southern Chinese population. [Methods] Survivin-31C/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorpbism (PCR-RFLP) in 711 healthy controls and 702 CRC cases. [Results] The number of CRC patients carrying with CC genotype was much higher than those of controls (36.5 % vs. 26.12%, X~2=17.89, P<0.001). Compared with CC genotypes, CG, GG genotypes and G allele carriers had a significantly decreased risk of CRC, with the decrease being 0.61-fold (95% CI=0.46-0.81, P<0.001), 0.52-fold (95% CI=0.38-0.71, P<0.001) and 0.58-fold (95% CI=0.45-0.74, P<0.001), respectively. [Conclusion] Survivin gene -31C/G polymorphism is associated with sporadic CRC risk, the G variant genotypo is the independent protective factors against sporadic CRC in soutbem Chinese population.

AIM: To investigate the association between -31C/G polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population. METHODS: survivin -31C/G genotypes were determined by PCR-RFLP in 711 healthy controls and 702 CRC cases. RESULTS: The number of CRC patients carrying with CC genotype was much higher than that of controls (36.5 % vs 26.2%,χ~2 =17.89,P<0.01). Compared to CC genotypes, CG, GG genotypes and G allele carriers had a significantly decreased risk of CRC, with the decrease being 0.61-fold (95% confidence interval=0.46-0.80, P<0.01), 0.52-fold (95% confidence interval=0.38-0.71,P<0.01) and 0.58-fold (95% confidence interval=0.45-0.74, P<0.01), respectively. CONCLUSION: survivin gene -31C/G polymorphism is associated with sporadic CRC risk, the G variant genotype is the independent protective factors against sporadic CRC in southern Chinese population.

Objective To detect the association between rs4646999 polymorphisms in the promoter region of the c-Jun and the prognosis of sporadic colorectal cancer. Methods rs4646999-673C>T genetypes were deter-mined by Taqman-MGB probes in 436 colorectal cancer cases. The survival curve was analyzed by Kaplan-Meier analysis and Cox regression.Western blot was used to analyze the expression levels of c-Jun protein in different gen-otypes. Results Univariate analysis showed that the cumulative survival rate of patients with rs4646999TT geno-type was significantly higher than that of patients with CT and CC genotype. Multivariate Cox regression analysis showed that the differentiation,lymph node metastasis,distant metastasis,TNM stage and rs4646999 genetypes were prognostic factors.Compared with the carriers of TT genotype,CT/CC complex genotypes were associated with poor prognosis of colorectal cancer(P<0.05).Protein expression analysis showed that the expression of c-Jun pro-tein in CC genotype was increased.In contrast,the TT genotype was decreased.Conclusions This study provided the evidence that rs4646999-673C>T genetic variant in c-Jun promoter regions is associated with the poor survival prognosis of colorectal cancer,possibly by elevating the protein expression levels that appeared to up-regulate activ-ity of c-Jun thus tumorigenesis.

Background Oral exposure to hexavalent chromium [Cr(VI)] can lead to gastrointestinal tumorigenesis in mice, and the mechanism is not yet clear. To predict health risk due to chemical exposure, data mining and computational toxicology analysis has become an important tool in toxicology research, which can help to elucidate mode of action (MOA) and identify key toxicity pathways. Objective This study aims to identify and evaluate key events in the MOA of oral Cr(VI) exposure. Methods Gene sets established from Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) respectively were imported into Ingenuity® Pathway Analysis (IPA) software for pathway enrichment analysis and biological function analysis to identify potential key toxicity pathways of target organs/tissues toxicity of oral exposure to Cr(Ⅵ). Next, the weight of evidence (WOE) of the identified key toxicity pathways in the MOA of oral exposure to Cr(VI) was evaluated based on the modified Bradford Hill principle. Results A total of 54 pieces of literature related to oral Cr(VI) exposure were screened in CTD, among which 18 and 9 were related to liver and intestine with 125 and 272 corresponding genes, respectively. The pathway enrichment and biological function analysis results showed that liver and intestinal perturbation pathways were mainly related to cell stress and injury, cell cycle regulation, and apoptosis, indicating that Nrf2 pathway and AHR pathway might be the key toxicity pathways involved in the cytotoxic-mediated MOA. Meanwhile, the dose (≥170 mg·L⁻¹ sodium dichromate) and the time point (90 d) of the activation of Nrf2 pathway was similar to the emergence of crypt cell proliferation. It was proposed that Nrf2 pathway activation might be a key event for cytotoxic-mediated MOA of small intestinal tumors. The WOE results showed moderate validity of evidence in this hypothesis, with high validity of evidence for biological plausibility and dose-response manner. Conclusion Nrf2 pathway activation might be the key event in the cytotoxic-mediated MOA of small intestinal tumors induced by oral exposure to Cr(VI) via initiating or maintaining crypt cell proliferation.