Estrogen receptor‐β gene polymorphism and colorectal cancer risk: Effect modified by body mass index and isoflavone intake

Estrogen receptor (ER)‐β signaling has generally been implicated in protection against colorectal cancer. The ER‐β gene cytosine‐adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community‐based case‐control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein‐labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age‐adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m^?2) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.     

L-MYC and GSTM1 polymorphisms are associated with unfavourable clinical parameters of gliomas

L-MYC and GSTM1 genotypes were analysed in glioma patients (GP) and healthy donors (HD). None of these genes appeared to influence the risk of this disease, however both polymorphisms correlated with unfavourable clinical parameters of gliomas. In particular, S allele of the L-MYC was overrepresented in the relapsed patients (P < 0.05), and GSTM1-null genotype was associated with the advanced tumour grade (P < 0.05). Patients, but not donors, demonstrated frequent combination of SS L-MYC homozygosity with GSTM1(-) variant (P < 0.01 ), as well as a correlation between LL L-MYC homozygosity and GSTM1 (+) genotype (P < 0.05).     

The association between the poly(A) polymorphism in the VDR gene and cancer risk: a meta-analysis

The poly(A) polymorphism (L/S) in the VDR gene has been implicated in susceptibility of cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between the poly(A) polymorphism in the VDR gene and cancer risk by meta-analysis. We searched PubMed database, EMBASE database, CNKI database, and Wanfang database, covering all studies until January 22, 2013. Statistical analysis was performed by using the software Revman4.2 and STATA 10.0. A total 8,186 cancer cases and 8,685 controls in 19 case–control studies from 15 studies were identified for data analysis. The results suggested that the S allele carriers (SS?+?SL) did not have an increased or decreased risk of cancer when compared with the homozygote LL carriers (odds ratio (OR)?=?0.96, 95 % CI?=?0.87–1.06, P?=?0.43 for SS?+?SL vs. LL). In addition, in the subgroup analysis by ethnicity and cancer type, no significant association was found among Caucasians, African-Americans, prostate cancer, or breast cancer. This current meta-analysis suggested that the poly(A) polymorphism in the VDR gene may not contribute to the risk of cancer. Future studies are needed to validate our findings.     

L-myc and GSTM1 polymorphism in cerebral glioma

L-MYC and GSTMI polymorphisms were studied in glioma patients. L-MYC allele frequency in patients (L: 61/114 (54%); S: 53/114 (46%)) and controls (L: 108/204 (53%); S: 96/204 (47%)) was identical. S allele was associated with certain unfavourable clinical features of the disease. In particular, its frequency was 26/42 (62%) in relapse vs. 26/68 (38%) in relapse-free disease (p < 0.05). GSTMI "null" genotype was identified in both patients and healthy donors (48%). GSTMI-deficient genotypes were significantly predominant in patients with grade III-IV gliomas as compared with grade I-II tumors (p < 0.05). Patients, but not donors, frequently revealed a combination of SS L-MYC homozygosity and GSTMI (-) variant (p < 0.01) as well as an association of LL L0-MYC homozygosity and GSTMI (+) genotype (p < 0.05).     

胶质瘤中MicroRNA-184的表达及其预后价值

目的 研究人脑胶质瘤石蜡包埋组织（formalin-fixed paraffin-embedded, FFPE）中微小RNA-184（microRNA-184, miR-184）的表达及其与临床病理特征之间的关系,探讨其在预测胶质瘤患者预后中的价值。方法 采用微阵列芯片法和RT-PCR检测108例胶质瘤FFPE和32例正常脑组织中的miR-184表达,同时Kaplan-Meier法分析胶质瘤患者总生存期和无病生存期情况。结果 胶质瘤组织中miR-184的表达下调,并用RT-PCR进一步验证; miR-184低表达与WHO分级（P=0.007）、Karnofsky 评分（KPS）（P=0.029）、复发时间（P=0.037）和生存时间（P=0.019）显著相关;Kaplan-Meier 分析结果表明,miR-184低表达与高表达患者总生存期（OS）（P=0.001）和无病生存期（DFS）（P=0.006）差异有统计学意义,miR-184低表达患者预后较差。多因素分析显示胶质瘤中miR-184的差异表达是预测OS[风险比（HR）：7.52;95％CI：2.63~21.42;P=0.002]和DFS[HR：11.56;95％CI：5.17~25.93;P<0.001]的独立危险因素。结论 miR-184的表达与胶质瘤患者预后显著相关,表明miR-184可作为预测胶质瘤患者预后的独立标志物。     

L-myc Proto-oncogene alleles and susceptibility to hepatocellular carcinoma

A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility or prognosis for some tumors. Using a PCR-based RFLP assay on DNA extracted from peripheral blood samples, we determined the L-myc EcoRI genotype of patients with HCC, patients with other liver tumors, and healthy controls. In this polymorphism there are 2 alleles, L and S, which define 3 possible genotypes: LL, LS, and SS. While the genotype distribution of patients with other liver tumors and healthy controls do not differ from one another, both differ significantly from the genotype distribution of patients with HCC. This difference is primarily the result of a low frequency of the SS genotype among HCC patients compared to controls or other liver tumor patients. Persons with the SS genotype appear to be protected against HCC and have roughly one-ninth the risk of persons who carry one or more copies of the L allele. Within HCC cases, patients with different L-myc genotypes show slight, but not statistically significant, differences in tumor characteristics and survival.     

Association between androgen receptor gene CAG repeat polymorphism and breast cancer risk: a meta-analysis

Androgens have been hypothesized to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol and their binding to the estrogen receptor and/or androgen receptor (AR) in the breast. The CAG repeat polymorphism in AR exon 1 has been implicated in breast cancer risk; however, studies on the association between this polymorphism and breast cancer risk remain conflicting. In order to derive a more precise estimation of the relationship, a large population-based case–control study was performed. We found that a long CAG sequence has a protective effect on breast cancer using an a priori determined cutoff (<22 or ≥22) in a dominant model analysis [SL–LL vs. SS, odds ratio (OR) = 0.86, 95% confidence intervals (CI): 0.67–1.10]. A similar result was obtained by analyzing seven detailed genotyping case–control studies by allele comparison in dominant and recessive models. However, larger scale primary study is required to further evaluate the interaction of AR CAG polymorphism and breast cancer risk.     

Hypermethylation of promoter 5＇CpG island of p16 gene in glioma tissue and plasma

ObjectiveTo explore the clinical significance of methylation status of promoter CpG island of p16 gene in glioma tissue and plasma.MethodsMethylation specific polymerase chain reaction (MSP) was used to determine the methylation status of the promoter for p16 gene within glioma tissue and plasma.Immunohistochemicel method (SP) was used to analyze the expressions of p16 and Ki-67 proteins.ResultsHypermethylation was found in 17/40 (42.5%) of brain gliomas,in comparison with 11/40 (27.5%) plasma specimens (x2 = 1.9780,P = 0.1596).Loss of p16 expression was associated (P = 0.0229) with hypermethylation of CpG island of promoter regions.Hypermethylation of p16 gene CpG island was significantly related to the increase of malignant grade of brain glioma (TissueX2 = 11.4288,P = 0.0007;PlasmaX2 = 8.9439,P = 0.0028).The Ki-67 index increased significantly (P＜0.05) in brain gliomas methylated in contrast to those unmethylated.ConclusionP16 hypermethylation may be one of the major mechanisms of tumorigenesis of gliomas.Methylated tumor-specific DNA may be as a plasma biomarker for prognosis in patients with glioma.     

287例盆腔及腹主动脉旁淋巴结清扫术与卵巢上皮性癌生存预后的临床分析

Objective: To evaluate the relationship between the pelvic and para-aortic lymphadenectomy and the prognosis of epithelial ovarian cancer. Methods: 287 patients suffering from primary epithelial ovarian cancer from 1995 to 2005 were analyzed retrospectively. Results: The 3-, 5-, 10-year survival with systematic lymphadenectomy (SL) were slightly higher than those without SL, but there were no statistically significance (P ＞ 0.05). The 3-, 5-, 10-year survival of clinical stages without SL were lower than those with SL, but there were no significant difference either (P ＞ 0.05). The 3-,5-, and 10-year survival rates with SL were higher than those without SL with no statistically differences (P ＞ 0.05) among the subgroups such as absent, ≤ 2 cm and ＞ 2 cm residual tumor. The survival rates of the groups without residual tumor and the group with ≤ 2cm residual tumor were significantly higher than that of ＞ 2 cm (P ＜ 0.005). On multivariate analysis, patient staging (P = 0.01)and size of residual disease after primary cytoreductive surgery (P ＜ 0.001 and = 0.002, respectively) retained prognostic significance. SL was not proved to be an independent prognostic factor (P = 0.69). Conclusion: Systematic pelvic and paraaortic lymphadenectomy can not improve and prolong the survival time significantly.     

Phase I clinical trial of all-trans-retinoic acid with correlation of its pharmacokinetics and pharmacodynamics

 A phase I trial of all-trans-retinoic acid (ATRA) was conducted to establish the maximum tolerable dose (MTD) of ATRA given once daily to patients with solid tumors. Cancer patients for whom no standard therapy was available were treated with ATRA once daily. Doses were escalated in cohorts of at least three patients. The pharmacokinetics of ATRA were assessed on day 1 for all patients and weekly for 31 patients who received doses of ≥110 mg/m² per day. Patients were followed for toxicity and response. Correlations of toxicity frequency and grade with pharmacokinetic parameters were sought. In addition, correlation of changes in ATRA pharmacokinetics with the concentration of ATRA metabolites in plasma were sought. A total of 49 patients received ATRA at doses ranging from 45 to 309 mg/m² per day. Hypertriglyceridemia was dose-limiting at 269 mg/m² per day. Other frequent toxicities included mucocutaneous dryness and headache. With chronic dosing, plasma ATRA concentrations fell in 59% of patients. Stable, low, or variable [ATRA] were seen in 16%, 6%, and 16% of patients respectively. Age, gender, smoking, or concurrent medication did not correlate with the pharmacokinetic pattern. Severe toxicities tended to occur with initial peak [ATRA] of ≥0.5 μg/ml (1.7 μM), and the toxicity frequency did not change if [ATRA] decreased with continued dosing. No consistent change in 4-oxo-ATRA or retinoid glucuronide concentrations was observed with decreases in plasma [ATRA]. The recommended once-daily ATRA dose is 215 mg/m², although significant interpatient variability is observed in toxicity and plasma retinoid concentrations. Although not statistically significant, more frequent and severe toxicity tended to occur in patients with higher plasma peak ATRA concentrations. Other factors, such as responses at target tissues, may be at least as important as the plasma ATRA concentration in predicting toxicity and/or response. Received: 7 January 1996 / Accepted: 24 June 1996     

PAX8 regulates telomerase reverse transcriptase and telomerase RNA component in glioma

Paired box (PAX) developmental genes are frequently expressed in cancers and confer survival advantages on cancer cells. We have previously found that PAX genes are deregulated in glioma. We have now investigated the expression of PAX genes in glioma and their role in telomere maintenance. The mRNA level of PAX8 showed a positive correlation with telomerase activity in glioma biopsies (r(2) = 0.75, P < 0.001) and in established glioma cell lines (r(2) = 0.97, P = 0.0025). We found that PAX8 is able to coordinately transactivate the promoter for both the telomerase catalytic subunit (hTERT) and the telomerase RNA component (hTR) genes. By electrophoretic mobility shift assay, quantitative PCR, and a telomerase activity assay, we show that PAX8 binds directly to the hTERT and hTR promoters, up-regulating hTERT and hTR mRNA, as well as telomerase activity. Additionally, PAX8 small interfering RNA down-regulated hTERT and hTR. Collectively, these results show that PAX8 may have a role in telomerase regulation.