| Objective:It is estimated thatglioma account for 80% of the nervous system tumors,and the most malignant form of gliomas with a mean patient survival after diagnosis of about 14 months. Despite standard treatment involving surgical resection, radiation therapy and chemotherapy, only very few patients survive more than 5 years. Many environ-mental and lifestyle factors including several occupations, Ionizing radiation, cellular phones, smoking, and diet have been considered to be associated with an increased glioma risk. However, the mechanisms underlying glioma tumorigenesis remain poorly understood. Not all individuals who are exposed to high doses of ionizing radiation and other risk factors of gliomas developed gliomas, which suggest that genetic factors may contribute to the development of glioma.Increasing evidences have reported that inherited risks may play an important role in the susceptibility to glioma,EFEMP1 is located in chromosome 2 and encodes a member of the fibulin family of extracellular matrix glycoproteins. Like all members of this family, the encoded protein contains tandemly repeated epidermal growth factor-like repeats followed by a C-terminus fibulin-type domain. Different members of the fibulin family showed different functions, either tumor-suppressive or oncogenic activity, including its roles in prostate cancer and glioma, have been reported. EFEMP1 suppressed glioma growth by modulating EGFR and AKT signaling pathway or promoted growth through the regulation of Notch pathway were identified.So far, only one study reported the association between EFEMP1 variations and risk of glioma. Therefore,four common SNPS of Efemp-1 were detected by PCR-RFLP. We aimed to explore the association of EFEMP1 rs3791679 polymorphism with glioma genetic susucetibility in a Chinese Han population. This study intends to adopt case-control, and collected 159 glioma cases and 364 controls in our hospital.Methods:(1) The study was based on the case-control retrospective method.. A group of 364 control subjects was randomly selected from the trauma outpatients and the annual check-up visitors in our hospital during July 2012 and June 2014. All the control subjects were free of glioma. The controls with a self-reported history of cancer or central ner-vous system-related diseases and previously receiving radiotherapy and chemotherapy for certain diseases were excluded from this hospital.At recruitment, all participants were inter-viewed by trained nurses to collect detailed demographic information, such as smoking, drinking and family history of cancer. The clinical characteristics of patients with glioma were collected from medical records, such as histology types and tumor grade.(2) The rs3791679, rs1346786, rs1344733 and rs727878 gene polymorphisms were analyzed using a poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The primers of rs3791679, rs 1346786, rs 13447-33 and rs727878 were designed using the Sequenom Assay Design 3.1 software.(3) The demographic and clinical characteristics of patients with glioma and control subjects were expressed by mean ± standard deviation or frequency and percentage. The differences between groups were compared by the t-test and chi-square test. The goodness-of-fit χ2-test was taken to analyze the departures from the Hardy-Weinberg equilibrium (HWE) of genotype distributions in rs3791679, rs1346786, rs13-44733 and rs727878. Unconditional logistic regression analysis was taken to analyze the association between rs3791679, rs1346786, rs1344733 and rs727878 polymorphisms and development of glioma, and the results were evaluated using the Odd’s ratio (OR) and 95% confidence interval (95% CI). The major homo-zygous genotypes of the rs3791679, rs 1346-786, rs 1344733 and rs727878 polymorphism were used as references. The interaction bet ween gene polymorphism and environmental factors in the risk of glioma was analyzed using multiple logistic regression analysis. Statisti-cal analysis was conducted using the SPSS 17.0 package (SPSS Inc., Chicago, IL, USA). P<0.05 was considered to indicate a significant difference.Results:(1) The demographic and clinical characteristics of patients with glioma and control subjects. The mean ages of patients with glioma and control subjects were 57.32±11.70 and 55.14±12.10, respectively. By a comparison of the demographic characteristics between patients and controls, we found no significant difference between the two groups. Of the 159 patients with glioma,52 (32.70%) patients were glioblastoma,107 (67.30%) were astrocytoma; oligodendroglioma and mixed glioma, 66 (41.51%) were at Ⅰ-Ⅱ tumor stage and 93 (58.49%) were at Ⅲ-Ⅳ tumor stage.(2) The information of the four common SNPs in EFEMP1 was shown in Table 2. By x2-test, we found a significant difference in the genotype distribution of rs3791679 between patients and controls (x2=7.37, P=0.03). By the goodness-of-fit x2-test, we found that the genotype distributions of rs3791679, rsl346786, rs13 44733 and rs727878 were in line with Hardy-Weinberg equilibrium, and the P values were 0.17,0.76,0.83 and 0.80, respectively (Table 2). Moreover, the minor allele frequencies of rs3791679, rs 1346786, rs 1344733 and rs727878 were similar with those in dbSNP databases.(3) By unconditional logistic regression analysis, we found that individuals carrying the AA genotype and GA+AA genotype were associated with development of glioma when compared with the GG genotype, and the adjusted ORs (95% CI) were 2.13 (1.15-3.90) and 1.55 (1.04-2.32), respectively. However, we did not find that rs1346786, rs1344733 and rs727878 were significantly associated with development of glioma.(4) GA+AA genotype of rs3791679 was associations with a heavy increased risk of glioma in patients who have family history of cancers, and the OR (95% CI) was 6.81 (1.17-48.06) (Table 4). However, we did not find significant association of rs3791679 polymorphism with smoking status and drinking status in the risk of glioma.(5) Conclusion:our study suggested an association between the rs3791679 polymorphism and an elevated risk of glioma; in addition, rs3791679 interacts with the family history of cancer in contributing to the development of glioma。Conclusion:1、our study suggested an association between the rs3791679 polymorphism and an elevated risk of glioma; in addition, rs3791679 interacts with the family history of cancer in contributing to the development of glioma。... |
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