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Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk-associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, p meta = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, p meta = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma., (© 2019 UICC.)

This study aims to investigate the associations of O 6 -methylguanine-DNA methyltransferase (MGMT) genetic polymorphisms (Leu84Phe and Ile143Val) with temozolomide (TMZ) resistance and prognosis of patients with malignant gliomas. A total of 212 patients diagnosed with malignant gliomas were enrolled in this study as the case group. All of these patients took oral TMZ and were assigned into the TMZ-sensitive (complete response+partial response) and the TMZ-resistant (stable disease+progressive disease) groups based on the clinical response after chemotherapy. The polymerase chain reaction-restriction fragment length polymorphism was used to identify the gene polymorphism of Leu84Phe and Ile143Val. The survival time and survival outcomes of all the patients were obtained by follow-up. There were significant differences in the genotype and allele of Leu84Phe between the TMZ-sensitive and the TMZ-resistant groups. The CT, TT and CT+TT genotypes and the T allele of MGMT gene Leu84Phe may be associated with increasing TMZ resistance in patients with malignant gliomas. Logistic regression analysis showed that Leu84Phe of MGMT gene and pathological grade were independent risk factors for the increase of TMZ resistance in patients with malignant gliomas. Kaplan-Meier survival curve revealed that the average survival time of patients with the CT+TT and CC genotypes of Leu84Phe in the two groups was statistically significant. COX regression analysis showed that Leu84Phe, degree of resection and pathological grade were independent prognostic factors for patients with malignant gliomas. Our study demonstrates that Leu84Phe of MGMT gene might be a risk factor of TMZ resistance and poor prognosis of patients with malignant gliomas.

The association between the CCDC26 rs4295627 single nucleotide polymorphism (SNP) and the glioma risk has been studied previously, but these studies have yielded conflicting results. The aim of the present study is to analyze this association more vigorously, by means of a meta-analysis. A comprehensive literature search was performed in databases PubMed and EMBASE. Six articles including 12 case-control studies in English with 11,368 controls and 5891 cases were eligible for the meta-analysis. We conducted subgroup analyses by the source of controls, ethnicity, and country. Our meta-analysis revealed that the rs4295627 SNP was associated with the glioma risk in a heterozygote model (TG versus TT: odds ratio = 1.35, 95% confidence interval = 1.26-1.45, P = 0.066). Moreover, our results suggested that the rs4295627 SNP was associated with a notably increased risk of glioma among Caucasians except for Swedes in 4 models (the homozygote model, recessive model, dominant model, and additive model). Nonetheless, in Sweden and China, the results showed no associations. No evidence of the publication bias was uncovered. Thus, our meta-analysis suggests that the rs4295627 SNP is associated with an increased risk of glioma. Additional studies are needed to derive more precise conclusion.

Accumulating evidence demonstrates that defining molecular subtypes based on objective genetic alterations may permit a more rational, patient-specific approach to molecular targeted therapy across various cancers. The objective of this study was to subtype primary glioblastoma (pGBM) based on MicroRNA (miRNA) profiling in Chinese population. Here, miRNA expression profiles from 82 pGBM samples were analyzed and 78 independent pGBM samples were used for qRT-PCR validation. We found that two distinct subgroups with different prognosis and chemosensitivities to temozolomide (TMZ) in Chinese pGBM samples. One subtype is TMZ chemoresistant (termed the TCR subtype) and confers a poor prognosis. The other subtype is TMZ-chemosensitive (termed the TCS subtype) and confers a relatively better prognosis compared with the TCR subtype. A classifier consisting of seven miRNAs was then identified (miR-1280, miR-1238, miR-938 and miR-423-5p (overexpressed in the TCR subtype); and let-7i, miR-151-3p and miR-93 (downregulated in the TCR subtype)), which could be used to assign pGBM samples to the corresponding subtype. The classifier was validated using both internal and external samples. Meanwhile, the genetic alterations of the TCR and TCS subtypes were also analyzed. The TCR subtype was characterized by no IDH1 mutation, and EGFR and Ki-67 overexpression. The TCS subtype displayed the opposite situation. Taken together, the results indicate a distinct subgroup with poor prognosis and TMZ-chemoresistance.

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

Objective: Brain metastasis as the first symptom of lung cancer is a unique clinical entity. We conducted a retrospective study to investigate the clinical characteristics and survival of patients with lung cancer whose first symptom was brain metastases in an Asian population., Methods: A retrospective study of 186 such patients who had been admitted to one institution in China between January 1, 2003 and December 30, 2008 was performed. The following data were collected and analyzed: manifesting signs and symptoms, imaging studies, extracerebral metastases, initial diagnosis, treatment, and patient survival., Results: This sample population exhibited high rates of misdiagnosis upon initial presentation (46.8 %). Fifty-seven (30.6 %) patients presented with silent extracerebral metastases. Pathologies among this cohort varied, and adenocarcinomas were most commonly observed. Most patients received surgical resection, and some patients had additional whole-brain radiotherapy or stereotactic radiosurgery. The median survival time for the entire cohort was 15 months (95 % confidence interval, 12.9-17.1 months). Survival rates for 1, 2, and 5 years were 58.2, 34.2, and 6.5 %, respectively. The median survival time was 15, 14, 19, and 7 months for the gross total resection, incomplete resection, surgery + whole-brain radiotherapy, and surgery + stereotactic radiosurgery groups, respectively., Conclusions: Brain metastasis as the first symptom of lung cancer is a distinct clinical entity. Although overall survival was poor, combined treatments based on surgery for selected patients were reasonable with the exception of a minority who experienced long-term survival.

Tumor angiogenesis, which is an important step in the development of cancer, is directly regulated by vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we examined the association of five potentially functional VEGFR-2 polymorphisms with glioma risk in a Chinese Han population. Three SNPs, rs2071559, rs7667298 and rs2305948, showed a statistically significant increased association with the risk of glioma (P = 0.006, 0.005, and 0.012, respectively). Both haplotype and diplotype analyses consistently revealed that subjects carrying two copies of the haplotype "CGT" had a 42% reduced glioma risk compared with their respective noncarriers. Our findings suggested that VEGFR-2 gene variants might contribute to glioma susceptibility.

It has been reported that IDH1 (IDH1R132) mutation was a frequent genomic alteration in grade II and grade III glial tumors but rare in primary glioblastoma (pGBM). To elucidate the frequency of IDH1 mutation and its clinical significance in Chinese patients with pGBM, one hundred eighteen pGBMs were assessed by pyro-sequencing for IDH1 mutation status, and the results were correlated with clinical characteristics and molecular pathological factors. IDH1 mutations were detected in 19/118 pGBM cases (16.1%). Younger age, methylated MGMT promoter, high expression of mutant P53 protein, low expression of Ki-67 or EGFR protein were significantly correlated with IDH1 mutation status. Most notably, we identified pGBM cases with IDH1 mutation were mainly involved in the frontal lobe when compared with those with wild-type IDH1. In addition, Kaplan-Meier survival analysis revealed a highly significant association between IDH1 mutation and a better clinical outcome (p = 0.026 for progression-free survival; p = 0.029 for overall survival). However, in our further multivariable regression analysis, the independent prognostic effect of IDH1 mutation is limited when considering age, preoperative KPS score, extent of resection, TMZ chemotherapy, and Ki-67 protein expression levels, which might narrow its prognostic power in Chinese population in the future.

The incidence of brain metastasis (BM) from colorectal carcinoma (CRC) is increasing. The objectives of the present study were to explore the clinical characteristics and potential prognostic factors in CRC patients with BM. Between April 1991 and December 2010, all CRC patients treated in the Sun Yat-sen University Cancer Center were retrospectively reviewed and 60 patients were identified to have BM (36 males and 24 females). The association between patients and their tumor characteristics, treatment modality, and survival were statistically analyzed. The median age at diagnosis of BM was 62.5 years. Fifty-three patients (88.3%) developed extracranial metastases at diagnosis of BM. The cause of death was systemic disease in 19 patients and neurological disease in 23 patients. Brain metastases were primarily treated with either whole brain radiation therapy (WBRT; 15 patients), stereotactic radiosurgery (SRS; nine patients), or surgical resection (seven patients). Ten patients received WBRT and SRS, and 19 patients (31.7%) were treated with steroids alone. The median survival after diagnosis of BM was 8 months (95% confidence interval = 4.2-11.8 months). Recursive partitioning analysis (RPA) class, the number of brain lesions, and treatment modality type were significantly associated with survival. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. A low RPA class and a limited number of brain lesions may predict increased survival after therapy for CRC patients with BM.

Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, -4q, -10q, +7p, and -15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Background: Epidermal growth factor (EGF) is critical in cancer process. EGF and EGF receptor (EGFR) interaction plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variations of the EGF +61G/A (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to brain glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population., Methods: In this study, we analyzed single nucleotide polymorphism of EGF +61G/A in 677 patients with glioma and 698 gender- and age-matched controls. Genotyping was performed by polymerase chain reaction-ligation detection reaction (PCR-LDR) method., Results: The A allele (minor Allele) was 33.0% in cases and 27.3% in controls. The additive model was more powerful to reveal the association in our study than that of recessive and dominant model. Our data showed the genotype G/A and A/A was associated with increased risk for glioma (adjusted OR = 1.48, 95%CI: 1.17-1.87, p = 0.001 for G/A, adjusted OR = 1.81, 95%CI: 1.20-2.72, p = 0.005 for A/A, respectively), and for glioblastoma (adjusted OR = 1.51, 95%CI: 1.06-2.17, p = 0.024 and adjusted OR = 2.35, 95%CI: 1.34-4.15, p = 0.003, respectively). The A allele significantly increased glioma risk (OR = 1.31, 95%CI: 1.11-1.55, p = 0.001). The additive model (G/G vs G/A vs A/A) showed that both G/A and A/A genotype increased glioma risk (adjusted OR = 1.40, 95% CI: 1.17-1.66, p = 0.0002).G/A and A/A genotypes or EGF +61 A allele increased risk in both low and high WHO grade glioma. Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers., Conclusions: Our study indicated that G/A and A/A genotypes or EGF +61 A allele were associated with higher glioma risk in Chinese. This is in contrast with previous studies which reported G allele as a risk factor of glioma in Caucasian. The role of EGF +61 A/G polymorphism in glioma susceptibility needs further investigation.

We have re-examined histopathological specimens of brain tumors extirpated at China Medical University from May, 1990 to June, 1992. During the last 2 years, about 400 cases of brain tumors were operated and 349 cases were histopathologically diagnosed and classified by one of the authors (T. I). The most common tumor was meningioma, 97 cases, followed by gliomas, 87 case and neurinoma, 71 cases. The sex and age distributions of these three tumor types were compared to those of Kyushu University Hospital, Japan. The most striking difference was age of meningioma and neurinoma patients, and Chinese patients were 10 years younger than Japanese patients. The incidence of 30th age group of meningioma was 25% in China and 10% in Japan. Thirty percent of neurinoma patients were operated at 30th and 40th age in China and Japan, respectively. The sex and ages of astrocytoma patients were almost the same frequencies in China and Japan. Among 22 cases of congenital tumors, 11 cases of epidermoid tumor in cerebello-pontine cistern was included. Cerebral tuberculoma, although rarely encountered in Japan, was 2 cases in China.

One hundred and sixty-eight cases of tumours of the central nervous system (CNS) from Chinese patients in Hong Kong were reviewed histologically as well as by the immunoperoxidase techniques in equivocal cases. Detailed comparisons were made between this series and previously published series on CNS tumours in Chinese, in other Asians and in Caucasians. The percentage of gliomas was low, and the average age of patients with high grade astrocytomas was low. Meningiomas were relatively common tumours and microcystic meningiomas were a common histological subtype. The percentages of vascular malformations and haemangioblastomas were also higher than those recorded in the West. The difference in incidence in gliomas and vascular malformations between this series and previous reports from mainland China was attributed to a possible difference between southern and northern Chinese.