The CASP-8 Promoter-652 6N Ins/del Polymorphism And A T/C Polymorphism Of MicroRNA196α-2 Genome Region And Glioma Risk In A Chinese Han Population

Gliomas are the most invasive tumor to human. Gliomas account for almost 80% of primary malignant brain tumors, and they result in more years of life lost than do any other tumors. Glioblastoma, the most common type of glioma, is associated with very poor survival, so glioma epidemiology has focused on identifying factors that can be modified to prevent this disease. Only two relatively rare factors have so far been conclusively shown to affect glioma risk-exposure to high doses of ionizing radiation, and inherited mutations of highly penetrant genes associated with rare syndromes. Recent research has focused on identifying germline polymorphisms associated with risk of glioma, and using molecular markers to classify glial tumors into more-homogenous groups. It concludes that endocardial gene mutations and genetic factors probably have a key effect on the occurrence of gliomas.Outside intervention factors will result in DNA sequence variation of organism will, such as single nucleotide polymorphism (SNPs). These variations can inherit stably which are associated with diseases. SNPs are most common in these variations. It is most possible genetics change that SNPs are associated with disease. Therefore, SNPs becomes the most commonly used tool which the research gene variation and disease occurs. With the tumor etiology progress, it is the biology universal foundation of occurrence of gliomas that oncogene is activated and tumor suppressor gene mutation. Generally thought, all the genes relevant to cancer etiology and progression are maybe concerned with the occurrence of gliomas.CASP-8 -652 6N ins/del polymorphism was firstly thought to be associated with the occurrence of multiple tumors. However, results of different studies showed to be inconsistent to establish a relationship between the variant and cancer susceptibility. Caspase-8 plays a key role in regulating apoptosis, and its functional polymorphism may alter apoptosis as well as cancer risk. Some evidences suggested that caspase-8 was associated with etiology and progression of glioma. To investigate the association between CASP-8 -652 6N ins/del polymorphism and the risk of glioma, we executed the current study in the Chinese population by analysis of glioma patients and controls (n=670 and 680, respectively). The results revealed that although CASP-8 -652 6N ins/del variant was not significantly associated with glioma risk on the whole (P=0.597; OR=1.05). Results showed an increased glioma risk in dominant genetic model among subjects with family history of cancer with the OR being 2.36 (95% CI, 1.25-4.45). To address the association of CASP-8 -652 6N ins/del polymorphism to cancer, we also performed a meta-analysis and the results suggested that the polymorphism was associated with a decreased risk of multiple cancers in a worldwide population with the summary OR=0.92; P=0.04. A similar result was found in non-Asian populations with the summary OR=0.98; P=0.10, but not in Asian populations.MicroRNAs (miRNAs) are small non-coding RNAs which play important roles in regulation of eukaryotic gene expression. Aberrant expression and structure alternation of miRNAs are considered to participate in tumorigenesis and cancer development. Recently, different genotypes of miR-196a polymorphisms (SNP, rs11614913) were found to be associated with the lung cancer patients' survival and increased risk of breast cancer. To further investigate whether this polymorphism may influence glioma risk or not, we examined the SNP allele frequency in Chinese population. Our data shows the genotype CC of miR-196a (rsll614913) polymorphism is associated with decreased risk of glioma in the Chinese population (OR=0.74, 95% CI: 0.48-0.99). Compared with the results from previous studies in lung cancer and breast cancer, our data suggest a different genotype association in glioma. This may be related to the diversity on the tissue origin, tumor type, tumorigenesis and developing process.In brief, we study the gene variation in order to find the inherent rules of main gene variation and occurrence of gliomas. We hoped providing the scientific basis to glioma diagnosis and gene therapy and the significance clues to related molecular mechanism of etiology of glioma.