Genetic Variants in MMP9 and TCF2 Contribute to Susceptibility to Lung Cancer

Objective：The Wnt signaling pathway is crucial for pulmonary development and differentiation;dysregulation of the Wnt signaling pathway may impair lung function.Indeed,single nucleotide polymorphisms （SNPs） of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers.In this study,we aimed to evaluate the influence of SNPs in Wnt-related genes （TCF2,MMP9） on susceptibility to lung cancer.Methods：Polymorphisms of TCF2 rs4430796,MMP9 rs2250889,and MMP9 rs17576 were studied in Han Chinese subjects,including 135 patients with lung cancer and 176 controls,using the Sequenom MassARRAY platform.The association of genotypes with susceptibility to lung cancer was analyzed using odds ratio （OR）,with 95% confidence interval （95% CI） and χ2.Results：The three SNPs （rs4430796,rs2250889,and rs17576） were found to be significantly associated with an increased risk of lung cancer.The AA genotype and AG＋AA genotype of rs4430796 showed a significantly increased susceptibility to lung cancer compared with the GG genotype （adjusted OR=6.03,95% CI：1.30-28.09,P=0.022;5.55,95% CI：1.20-25.58,P=0.028）.Compared with the rs17576 GG genotype,the AG and AG＋AA genotypes were also associated with a significant risk （adjusted OR=2.65,95% CI：1.60-4.37,P≤0.001;2.57,95% CI：1.59-4.19,P≤0.001） whereas the rs2250889 CG and CG＋GG genotypes had 2.97-fold （95% CI：1.81-4.85;P≤0.001） and 2.80-fold increased associations with lung cancer （95% CI：1.73-4.54;P≤0.001）,respectively,compared with the rs2250889 CC genotype.Furthermore,the association of rs4430796 with lung cancer became insignificant （P0.05） after adjusting for gender and rs2250889.Conclusion：The three SNPs may play a role in the predisposition of members of the Han Chinese population to lung cancer.

Single-Nucleotide Polymorphism Associations for Colorectal Cancer in Southern Chinese Population

Objective： Genome-wide association studies （GWAS） have identified 11 loci that influence the risk of developing colorectal cancer （CRC）. Given that these studies were conducted in European Caucasian populations, it is not clear whether the results are relevant for populations with different ethnicities. The aim of this study was to examine these associations in a southern Chinese population. Methods： Eleven single-nucleotide polymorphisms （SNPs）, rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, were genotyped in 229 CRC patients and 267 controls using the MassArray SNP genotyping system. Results： Evidence of an association with CRC was found for four of the 11 loci. The strongest associations were with rs4444235 and rs961253, with significant odds ratios close to those reported in previous GWAS. Among these four loci, rs719725 and rs4444235 were significantly associated with female gender, rs3802842, rs961253, and rs4444235 with early disease onset, and rs3802842 with later disease onset. However, no associations with CRC risk were detected for six other loci （rs9929218, rs10411210, rs12701937, rs7014346, rs6983267, and rs10795668）, and one SNP, rs16892766, was not polymorphic in any of the study participants. Conclusion： The rs4444235 and rs961253 loci are strongly associated with the risk of CRC in southern Chinese.

Aberrant methylation and downregulation of sall3 in human hepatocellular carcinoma

AIM: To investigated whether sall3 transcription was regulated by promoter CpG island hypermethylation in hepatocellular carcinoma (HCC). METHODS: The cell lines Huh7, HepG2, SK-HEP1, SM-MC7721, Bel7402, QGY7703 and a cohort of 38 HCC tissue specimens and corresponding nontumorous tissues were subjected to analysis for sall3 promoter CpG island methylation and mRNA transcription. sall3 promoter CpG island methylation levels were determined using the MassARRAY platform and mRNA transcription levels of the gene were detected by quantitative realtime polymerase chain reaction.RESULTS: The levels of sall3 mRNA were decreased by more than twofold in 33 of 38 tumor tissues compared to adjacent noncancerous tissues. Among these 33 tumor tissues with lower levels of sall3 mRNA, 24 showed higher levels of methylation. Based on these results, we hypothesized that the decrease in sall3 mRNA transcription level was likely due to promoter CpG island hypermethylation. Changes in sall3 mRNA transcription and promoter CpG island methylation were determined in the above six cell lines after treatment with 0, 0.1, 0.5 and 2.5 mmol 5-aza-2-deoxycytidine, a demethylating agent. Promoter CpG island methylation levels de- creased in a dose-dependent manner in all six cell lines, while the mRNA transcription level increased dose-dependently in Huh7, HepG2, SK-HEP1 and SMMC7721 cells and irregularly in Bel7402 and QGY7703 cells. CONCLUSION: These results indicated that promoter CpG island hypermethylation contributes to the downregulation of sall3 mRNA transcription in HCC.