ABSTRACT
BACKGROUND: hTERT contains a high density of minisatellites, of which rare alleles of hTERT-VNTR2-2nd have been reported to be associated with prostate cancer. This shows an association between VNTR and cancer, but this repeat sequence is likely to be associated with genomic instability. Therefore, we investigated the effects of hTERT-VNTR2-2nd on gastrointestinal cancer and the relationship between repeated sequence and chromosome instability. METHODS: A case-control study was performed using DNA from 818 cancer-free controls, 539 cases with gastric cancer, 275 cases with colon cancer and 274 cases with rectal cancer. To determine whether minisatellites affect gene expression, expression levels were examined using TERT-reporter vectors in cell lines. In addition, the length of the hTERT-VNTR2-2nd alleles were determined in blood and cancer tissues from 107 gastric cancers, 112 colon cancers and 76 rectal cancers patients to determine whether the repeat sequence was associated with genomic instability during cancer development. RESULTS: No statistically significant association between hTERT-VNTR2-2nd and risk of gastrointestinal cancer was detected. However, it has been shown that VNTRs inserted into the enhancer region can regulate the expression of TERT in gastrointestinal cancer cells. Moreover, hTERT-VNTR2-2nd was analyzed in matched blood and cancer tissue from patients with gastrointestinal cancer and in seven among 294 subjects, and hTERT-VNTR2-2nd was found to be rearranged. CONCLUSIONS: We suggest that minisatellites are associated with genomic instability in cancer and that the hTERT-VNTRs region may increase hTERT expression in gastrointestinal cancer cells.
Subject(s)
Gastrointestinal Neoplasms/genetics , Genomic Instability , Minisatellite Repeats , Telomerase/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Cell Line, Tumor , Female , HEK293 Cells , Humans , Male , Middle Aged , Polymorphism, Genetic , Young AdultABSTRACT
Objective To investigate the association between the minisatellite polymorphism in the first exon of PLA2G4C gene and schizophrenia, and to reveal the important role of DNA sequence polymorphism in the pathogenesis of schizophrenia.Methods The minisatellite polymorphisms in the first exon of PLA2G4C gene in 91 patients with schizophrenia (case group)and 81 healthy persons (control group)were detected with PCR-sequencing analysis.The chi-square (χ2 )goodness-of-fit test was used to analyze the distribution of the PLA2G4C minisatellite polymorphism in various groups and to explore the association between the minisatellite polymorphism in the first exon of PLA2G4C gene and schizophrenia. Results There were minisatellite polymorphisms in PLA2G4C gene.Three kinds of polymorphisms 1×27 bp,2×27 bp and 3×27 bp were found by sequencing.The distribution of allelic frequencies at PLA2G4C polymorphism showed no statistical significance between case group and control group (P>0.05 ). No statistically significant difference was found in 3-homozygous haplotypes in PLA2G4C gene between case group and control group (P>0.05).At the same time,there was no statistically significant difference between 3-heterozygous haplotypes in PLA2G4C gene between case group and control group (P>0.05).Conclusion The minisatellite polymorphisms in the first exon of PLA2G4C gene are found,but the minisatellite polymorphism in the first exon of PLA2G4C gene may be not associated with the occurrence of schizophrenia.
