共查询到20条相似文献,搜索用时 453 毫秒
1.
Hildur Helgadottir Emilia Andersson Lisa Villabona Lena Kanter Henk van der Zanden Geert W. Haasnoot Barbara Seliger Kjell Bergfeldt Johan Hansson Boel Ragnarsson-Olding Rolf Kiessling Giuseppe Valentino Masucci 《Cancer immunology, immunotherapy : CII》2009,58(10):1599-1608
Purpose We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate
cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with
stage III–IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the
prognosis in stage III–IV malignant melanoma patients.
Patients and methods A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles
in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined
by Kaplan–Meier and Cox analysis.
Results The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival
rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02–4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype
(HR = 0.40; CI = 0.17–0.90; P = 0.02).
Conclusions Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour
control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding
poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between
tumour clones escape and immune surveillance ending up with a rapid disease progression.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
2.
CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers 总被引:5,自引:0,他引:5
Kono K Kawaida H Takahashi A Sugai H Mimura K Miyagawa N Omata H Fujii H 《Cancer immunology, immunotherapy : CII》2006,55(9):1064-1071
Purpose: Regulatory T cells (T regs) can inhibit immune responses mediated by T cells. It has been shown that there is an increased proportion of T regs in several different human malignancies, although the actual mechanism remains unclear. In the present study, we evaluated the prevalence of CD4(+)CD25high T regs in PBMCs from patients with gastric and esophageal cancers in relation to the clinical outcome. Methods: PBMCs in 72 patients with gastric cancer and 42 patients with esophageal cancer were evaluated for the proportion of CD4(+)CD25high T cells, as a percentage of the total CD4(+) cells, by flow cytometric analysis with triple-color staining. Actuarial overall survival rates of the patients were analyzed by the Kaplan–Meier method. Results: The percentages of CD4(+)CD25high T cells for cases of gastric cancer (4.9±1.2%) and esophageal cancer (5.2±2.1%) were significantly higher than those for healthy donors (1.9±1.1%, P<0.01). There were significant differences in the prevalence of CD4(+)CD25high T cells between the early and advanced disease stages, both in gastric cancer (stage I vs. III, P<0.05; stage I vs. IV, P<0.05) and esophageal cancer (stage I vs. IV, P<0.05). The patients with a high proportion of CD4(+)CD25high T cells showed poorer survival rates in comparison to those with a low proportion, in both gastric and esophageal cancers. After patients received curative resections of gastric cancers (n=57), the increased proportions of CD4(+)CD25high T cells were significantly reduced, and the levels were almost equal to those in normal healthy donors. In addition, studies of gastric cancer patients with postoperative recurrent tumors (n=6) revealed that the prevalence of CD4(+)CD25high T cells individually increased compared to 2 months after the operations. CD4(+)CD25high T cells expressed FOXP3 mRNA and had abundant CD45RO and intracellular CTLA-4 molecules. Conclusions: These results strongly suggest that tumor-related factors induce and expand CD4(+)CD25high T regs. 相似文献
3.
Ahmed W Malik M Saeed I Khan AA Sadeque A Kaleem U Ahmed N Ajmal M Azam M Qamar R 《Molecular biology reports》2011,38(4):2541-2548
A case–control association study on 229 Myocardial Infarction (MI) patients and 217 healthy controls was carried out to determine
the role of tissue-plasminogen activator (t-PA) (Alu-repeat insertion (I)/deletion (D)) and plasminogen activator inhibitor
(PAI-1) (4G/5G insertion/deletion) polymorphisms with MI in the Pakistani population. In MI patients the genotype distribution
of the PAI-1 gene was not found to be different when compared with the unaffected controls (P > 0.05, χ2 = 1.03). The risk allele 4G was also not associated with MI (P > 0.05, χ2 = 0.46, odds ratio (OR) = 1.1 (95% confidence interval (CI) = 0.84–1.43), P > 0.05). Similarly, the genotype frequencies of t-PA I/I, I/D and D/D were not different from the unaffected controls (P > 0.05, χ2 = 1.60), and the risk allele “I” was not found to be associated with MI (P > 0.05, χ2 = 1.35, OR = 0.86 (95% CI = 0.66–1.11), P > 0.05). However, when the data were distributed along the lines of gender a significant association of the 4G/4G PAI-1 genotype
was observed with only the female MI patients (P < 0.05, z-test = 2.21). When the combined genotypes of both the polymorphisms were analyzed, a significant association of
MI was observed with the homozygous DD/4G4G genotype (P < 0.01, z-test = 2.61), which was specifically because of the female samples (P = 0.01, z-test = 2.53). In addition smoking (P < 0.001, χ2 = 13.52, OR = 3.45 (95% CI = 1.77–6.94)), diabetes (P < 0.001, χ2 = 22.45, OR = 8.89 (95% CI = 2.96–29.95)), hypertension (OR = 7.76 (95% CI = 2.88–22.68), P < 0.001) family history (P < 0.001, χ2 = 13.72, OR = 3.7 (95% CI = 1.71–8.18)) and lower HDL levels (P < 0.05) were found to be significantly associated with the disease. In conclusion the PAI-1 gene polymorphism was found to
have a gender specific role in the female MI patients. 相似文献
4.
Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this
research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case–control study. The epidemiological
risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay
(ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological
data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers,
patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma
VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison
with controls (CT vs. CC, OR 2.00, 95% CI 1.23–3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28–3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25–2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C−/T−. CRA patients
with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying
936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The
VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility. 相似文献
5.
Xiang ZL Zeng ZC Fan J Tang ZY He J Zeng HY Chang JY 《Molecular biology reports》2012,39(2):2021-2029
The purpose of this study was to evaluate the relationship between hypoxia-inducible factor-1α (HIF-1α) protein expression
in hepatocellular carcinoma (HCC), and responses of abdominal metastatic lymph nodes (LNs) from HCC patients treated with
external beam radiotherapy (EBRT). HIF-1α immunohistochemical staining was performed on tissue microarrays (TMAs) of primary
HCC specimens from 69 HCC patients with abdominal LN metastases. All patients received abdominal metastatic LN EBRT at the
Department of Radiation Oncology at Zhongshan Hospital. A receiver-operating characteristic (ROC)-based approach and logistical
regression analysis were used to determine the predictive value of HIF-1α expression in primary tumors with HCC metastatic
LN EBRT response. Kaplan–Meier curves and log-rank tests were used to analyze patient survival. Cox proportional hazards regression
model was used to analyze independent prognostic factors. HIF-1α expression was correlated with blood hemoglobin (Hb: r = −0.280, P = 0.020), response of abdominal metastatic LNs to EBRT (r = 0.286, P = 0.017), locoregional recurrence (r = 0.278, P = 0.021), and cancer-specific deaths (r = 0.298, P = 0.013). HIF-1α expression was predictive of EBRT response of metastatic LNs [area under the curve (AUC): 0.646; 95% confidence
interval (CI): 0.499–0.793; P = 0.047], locoregional recurrence (AUC: 0.657; 95% CI: 0.509–0.805; P = 0.049) and cancer-specific deaths (AUC: 0.671; 95% CI: 0.531–0.812; P = 0.035). Patients with tumors exhibiting high HIF-1α expression had significantly poorer overall survival (OS) than those
with low tumor expression of HIF-1α (P = 0.016). Multivariate analysis showed that Hb (P = 0.035), vascular invasion (P = 0.026), Child-Pugh score (P < 0.001), intrahepatic tumor control (P < 0.001), and HIF-1α (P = 0.020) were independent prognosis factors for OS of HCC patients after receiving abdominal metastatic LN EBRT. HIF-1α expression
in primary HCCs was associated with EBRT response of abdominal metastatic LNs and poor prognosis. 相似文献
6.
P73 is a structural and functional homologue of p53, and plays an important role in regulating cell cycle and apoptosis. A
potentially functional polymorphism (designated as p73 G4C14-to-A4T14) has been identified in a region in exon 2 of the p73 gene, which may theoretically form a stem-loop structure and thereby affect p73 expression. Several investigations have reported the correlation between p73 G4C14-to-A4T14 polymorphism and cancer risk.
However, the results are inconclusive. To further assess the association between p73 polymorphism and cancer risk, we performed
meta-analysis of the data sets obtained from 26 individual studies involving 8,148 cancer patients and 8,150 controls. The
association between p73 G4C14-to-A4T14 polymorphism and cancer risk was determined by crude odd ratios (OR) with 95% CI (confidential
interval). AT-allele carriers were found to have a significantly increased risk of cervical cancer (AT/GC vs. GC/GC, OR = 1.63,
95% CI = 1.14–2.33; AT/AT + AT/GC vs. GC/GC, OR = 1.49, 95% CI = 1.05–2.10), colorectal cancer (AT/AT vs. AT/GC + GC/GC, OR = 1.98,
95% CI = 1.25–3.12), head and neck cancer (AT/AT + AT/GC vs. GC/GC, OR = 1.44, 95% CI = 1.06–1.96) and other cancers (AT/AT
vs. GC/GC, OR = 1.78, 95% CI = 1.24–2.57; AT/AT vs. AT/GC + GC/GC, OR = 1.80, 95% CI = 1.26–2.56). In the stratified analysis
of ethnicity, a significantly elevated cancer risk was found in Caucasians (AT/AT + AT/GC vs. GC/GC, OR = 1.18, 95% CI = 1.08–1.30;
allele AT vs. allele GC, OR = 1.15, 95% CI = 1.06–1.24). No significant association of p73 polymorphism with the cancer risk
of smoking was detected by stratified analysis by smoking status. Together, our data suggest that the p73 G4C14-to-A4T14 may
be a risk factor of cancer especially in Caucasians. 相似文献
7.
Meiyun Kang Xiaojie Ding Ming Xu Haixia Zhu Sang Liu Meilin Wang Dongmei Wu Na Tong Weida Gong Jianwei Zhou Zhengdong Zhang 《Gene》2014
A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P = 0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR = 1.41, 95% CI = 1.08–1.84 for cardia cancer and HR = 1.64, 95% CI = 1.14–2.37 for intestinal-type), tumor size ≤ 5 cm (HR = 1.41, 95% CI = 0.56–0.99), T1 depth invasion (HR = 2.34, 95% CI = 1.20–4.56), lymph node metastasis (HR = 1.51, 95% CI = 1.19–1.96), no distant metastasis (HR = 1.33, 95% CI = 1.05–1.68), TNM stage III + IV (HR = 1.50, 95% CI = 1.13–1.98), and with chemotherapy (HR = 1.53, 95% CI = 1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population. 相似文献
8.
Markovic S Antic J Dragicevic N Hamelin R Krivokapic Z 《Journal of molecular histology》2012,43(2):137-143
Microsatellite instability (MSI) is a genetic consequence of a MisMatch Repair defect in colorectal cancer (CRC). We compared
clinicopathohistological features with MSI status of CRC and evaluated prognostic significance of MSI status and BRAF mutation
in the group of MSI-H tumors. 155 primary CRCs were excised surgically, 2006–2008. MSI analysis was carried out using a fluorescence-based
pentaplex polymerase chain reaction technique. BRAF mutation (V600E) was analyzed by direct sequencing in MSI-H tumors. For
all patients were evaluated: age, gender, localization, tumor cell type, tumor differentiation, mucin production, lymphocytic
infiltration (TILs) and TNM stage. Patients’ disease-free survival (DFS) was compared according to MSI and BRAF status using
Kaplan–Meier test. Of the 155 CRCs, 19 (12.3%) were MSI-H, and 136 (87.7%) were MSS/L. BRAF mutations were found in 4 of the
MSI-H tumors. Patients with MSI-H CRC had lower recurrence rate (log rank test; P = 0.04) than MSS/L group. Patients with MSI-H tumor and BRAF mutation had worse DFS than MSI-H tumors without this mutation
(log rank test; P = 0.01). Most of the clinicopathologic characteristics of MSI-H CRC in Serbian patients are similar to those reported in
previous studies. Patients with MSI tumor phenotype had favourable prognosis, but in those with BRAF mutation higher recurrence
rate was observed. 相似文献
9.
The goal of this retrospective study was to determine the effect of para-aortic lymphadenectomy on clinical outcome in patients
with stage N+ rectal adenocarcinoma below the peritoneal reflection. A retrospective analysis was performed on the clinical
outcome of 181 patients with stage N+ rectal adenocarcinoma below the peritoneal reflection who underwent total mesorectal
excision (TME) with total pelvic lymph node (PLN) adenectomy, with or without para-aortic lymph node (PAN) adenectomy. Independent
prognostic factors were determined by multivariate Cox regression analysis. Disease-free survival (DFS) was analyzed using
Kaplan–Meier curves and the log-rank test. The incidence of PLN metastases was 39.2% (71/181) in all the patients, and the
incidence of PAN metastases was 12% (12/100) in patients who received PLN + PAN adenectomies. The patients were divided into
two groups: PLN adenectomy (n = 81) and PLN + PAN adenectomy (n = 100). There were no statistically significant differences in clinicopathological factors between the PLN adenectomy and
PLN + PAN adenectomy groups. On univariate analysis, the gross tumor type (P = 0.012), histological differentiation (P = 0.013), CEA level (P = 0.019), T stage (P = 0.019), N stage (P < 0.0001), and the number of positive PLN sites (P < 0.0001) were associated with poor DFS. Gross tumor type (P = 0.031), N stage (P = 0.001), and the number of positive PLN sites (P < 0.0001) were independent prognostic factors for DFS as identified by multivariate Cox regression analysis. PLN + PAN adenectomy
significantly improved DFS compared to PLN adenectomy alone in patients with noninfiltrating type (P = 0.001), but not in patients with infiltrating type (P = 0.075). PLN + PAN adenectomy significantly improved DFS compared to PLN adenectomy alone in patients with 0 or 1 positive
PLN site (P = 0.001, P = 0.009 respectively), but not in patients with ≥2 positive PLN sites (P = 0.095). In the N1 and N2 stage groups, PLN + PAN adenectomy significantly improved DFS compared with PLN adenectomy alone
(P = 0.001; P < 0.0001, respectively). Furthermore, mean DFS was longer in the absence of PAN metastasis (P < 0.0001). PAN metastases appear to be associated with reduced DFS. Total PAN adenectomy may improve DFS in patients with
noninfiltrating type, stage III rectal cancer below the peritoneal reflection, who have <2 positive PLN sites. 相似文献
10.
Thomas Josef Vogl Thaddäus T. Wissniowski Nagy N. N. Naguib Renate M. Hammerstingl Martin G. Mack Sabine Münch Matthias Ocker Deike Strobel Eckhart G. Hahn Johannes Hänsler 《Cancer immunology, immunotherapy : CII》2009,58(10):1557-1563
Purpose To asses if laser-induced thermotherapy (LITT) induces a specific cytotoxic T cell response in patients treated with LITT
for colorectal cancer liver metastases.
Methods Eleven patients with liver metastases of colorectal cancer underwent LITT. Blood was sampled before and after LITT. Peripheral
T cell activation was assessed by an interferon gamma (IFNg) secretion assay and flow cytometry. Test antigens were autologous
liver and tumor lysate obtained from each patient by biopsy. T cells were stained for CD3/CD4/CD8 and IFNg to detect activated
T cells. The ratio of IFNg positive to IFNg negative T cells was determined as the stimulation index (SI). To assess cytolytic
activity, T cells were co-incubated with human colorectal cancer cells (CaCo) and cytosolic adenylate kinase release was measured
by a luciferase assay.
Results IFNg secretion assay: before LITT SI was 12.73 (±4.83) for CD3+, 4.36 (±3.32) for CD4+ and 3.64 (±1.77) for CD8+ T cells against
autologous tumor tissue. Four weeks after LITT SI had increased to 92.09 (±12.04) for CD3+ (P < 0.001), 42.92 (±16.68) for CD4+ (P < 0.001) and 47.54 (±15.68) for CD8+ T cells (P < 0.001) against autologous tumor tissue. No increased SI was observed with normal liver tissue at any time point. Cytotoxicity
assay: before LITT activity against the respective cancer cells was low, with RLU = 1,493 (±1,954.68), whereas after LITT
cytolytic activity had increased to RLU = 7,260 [±3,929.76 (P < 0.001)].
Conclusion Patients with liver metastases of colorectal cancer show a tumor-specific cytotoxic T cell stimulation and a significantly
increased cytolytic activity of CD3+, CD4+ and CD8+ T cells after LITT against an allogenic tumor (CaCo cell line). 相似文献
11.
Arıkan S Cacina C Guler E Çulcu S Tuna G Yaylım-Eraltan I 《Molecular biology reports》2012,39(3):3245-3249
Endothelial nitric oxide synthase (eNOS), coded by the gene NOS3, may play an important role in uncontrollable cellular growth
in several cancer types. Our study was performed to test the association between Glu298Asp polymorphisms in the NOS3 gene
and colorectal cancer risk and progression. In this study, NOS3 Glu298Asp polymorphism was genotyped in 84 patients with colorectal
cancer and 99 healthy subjects using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis.
There were significant differences in the distribution of NOS3 genotypes and frequencies of the alleles between colorectal
cancer patients and controls (P = 0.016, P = 0.006, respectively). The increased frequency of NOS3 Glu298Asp homozygotes genotypes in patients who had advanced tumour
stage was statistically significant (P = 0.042). Our findings have suggested that NOS3 Glu298Asp polymorphism might be associated with the risk and progression
of colorectal cancer in Turkish population. 相似文献
12.
Thakur Hitender Gupta Lipsy Sobti Ranbir C. Janmeja Ashok K. Seth Amlesh Singh Sharwan K. 《Molecular biology reports》2011,38(3):1733-1739
The glutathione S-transferase (GST) family of enzymes is known to play a pivotal role in phase II of biotransformation of
xenobiotics, environmental carcinogens and pharmacological drugs. The objective of the present study was to investigate the
role of GSTM1 and GSTT1 null genotypes as risk factors for chronic obstructive pulmonary disease (COPD) and prostate cancer. The subjects appraised
were 200 COPD cases, 150 prostate cancer cases, 150 benign prostatic hyperplasia (BPH) cases, 200 age matched controls for
COPD and 172 age matched controls for prostate cancer. GSTM1 and GSTT1 null genotype was found to confer 2.5 (OR 2.45; 95% CI 1.56–3.82; P value = 0.00008) and 2.4-fold (OR 2.39; 95% CI 1.36–4.20; P value = 0.002) significant higher risk for prostate cancer. Smoking imparted a 2.2-fold significant risk of prostate cancer
cases (OR 2.23; 95% CI 1.36–3.65 P value = 0.001) and twofold risk in BPH (OR 2.09; 95% CI 1.26–3.46; P value = 0.005). In case of COPD only null genotype of GSTT1 has shown 2.1-fold (OR 2.11; 95% CI 1.22–3.62; P value = 0.007) significant increased risk. 相似文献
13.
Christoph Domschke Florian Schuetz Nora Sommerfeldt Joachim Rom Alexander Scharf Christof Sohn Andreas Schneeweiss Philipp Beckhove 《Cancer immunology, immunotherapy : CII》2010,59(3):479-486
Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they
can be reactivated to IFN-γ producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID
mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific
tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-γ
EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory
T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A*0201-restricted peptides from the tumor-associated antigens MUC1, Hpa16–24 and Hpa183–191 was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific
cellular immune responses in the human BM. 相似文献
14.
Zhang R Duan L Jiang Y Zhang X Sun P Li J Zhang M Tang G Wang X Li X 《Molecular biology reports》2011,38(8):5079-5084
Previously published analyses of the association between the interleukin 7 receptor (IL7R) T244I polymorphism (rs6897932) and multiple sclerosis (MS) have yielded conflicting results. We performed a meta-analysis
to assess whether the combined data showed this association, and to investigate its effect size. We analyzed 10 studies identified
from PubMed (12,185 MS patients and 15,855 controls) and calculated the odds ratios (ORs) and 95% confidence intervals (CIs)
for the C-allele, the C/C genotype (recessive effect) and the C/C + C/T (dominant effect) genotype. Heterogeneity within and
between studies was observed: allele C: Q = 30.86, P = 0.002; genotype C/C: Q = 30.28, P = 0.003. Using a random-effects model, the C-allele and the C/C genotype were associated with MS (OR = 1.11, 95% CI = 1.04–1.19,
P = 0.001 for the C-allele; OR = 1.15, 95% CI = 1.06–1.24, P = 0.0009 for the C/C genotype). The C/C + C/T genotype was also associated with MS using a fixed-effects model (OR = 1.15,
95% CI = 1.05–1.26, P = 0.003). There was no significant publication bias among the selected studies according to the funnel plot. We also performed
the analysis on a European subgroup. This revealed an association between IL7R T244I and MS (P < 0.00001 for the C-allele and the C/C genotype; P = 0.0004 for the C/C + C/T genotype), no heterogeneity was observed (allele C: P = 0.07; genotype C/C: P = 0.10). In conclusion, the meta-analysis demonstrated that the IL7R T244I polymorphism was associated with susceptibility to MS. 相似文献
15.
The results of studies on association between the C677T polymorphism of the 5,10-methylene-tetrahydrofolate reductase (MTHFR)
gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship
between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with
ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy–Weinberg equilibrium.
The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot,
Egger’s regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included.
Heterogeneity was observed (χ
2 = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92–2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population
for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21–2.43; P = 0.002; I
2
= 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66–1.66; P = 0.35; I
2
= 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When
stratifying for the race, this meta-analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism
and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated
studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility. 相似文献
16.
Espino-Paisan L de la Calle H Fernández-Arquero M Figueredo MA de la Concha EG Urcelay E Santiago JL 《Immunogenetics》2011,63(4):255-258
The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D). This result was confirmed by a follow-up study that
pointed to new independent signals within the region. However, both studies were performed in patients with an early-onset
T1D. We aimed at replicating the previous results and studying the influence of these polymorphisms in the age at T1D debut.
We genotyped 439 T1D Spanish subjects (age at onset, 1 to 65 years) and 861 controls for two PTPN2 single nucleotide polymorphisms (SNPs), rs2542151 and rs478582, and studied the effect of both polymorphisms in age at onset
through stratified and continuous analyses. The frequency of rs2542151*G carriers was significantly higher in the early-onset
group compared with late-onset patients (p = 0.023) and with controls (OR = 1.61 [1.14–2.26]; p = 0.005). No significant differences were found between controls and late-onset patients. The log-rank chi-square test for
the Kaplan–Meier plots (carriers of susceptibility allele vs non carriers) was statistically significant (χ
1df2 = 4.485; p = 0.034), yielding an earlier disease debut for G carriers. The analysis of the SNP rs478582 did not reach statistical significance.
In summary, we replicate the association detected by the WTCCC and propose that the rs2542151*G allele confers risk to an
earlier onset of T1D. 相似文献
17.
The aim of this study was to determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism
confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted
on the PTPN22 C1858T polymorphism involving eighteen studies, which in total contained 20344 RA patients and 21828 controls.
Meta-analysis revealed an association between the PTPN22 C1858T polymorphism T allele and RA in all subjects (odds ratio [OR] = 1.637,
95% confidence interval [CI] = 1.514–1.770, P < 0.001). After stratification by ethnicity, analysis indicated that the PTPN22 C1858T polymorphism T allele was significantly
associated with RA in Europeans and Non-Europeans (OR = 1.587, 95% CI = 1.486–1.696, P < 0.001; OR = 1.748, 95% CI = 1.274–2.398, P < 0.001). Meta-analysis of the CT + TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism
T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and -negative subjects revealed a significant
association with the T allele in RA patients with RF, but not in subjects without RF. In conclusion, this meta-analysis confirms
that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans,
and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients. 相似文献
18.
Background
NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case–control study to evaluate the potential association between NQO1 609C > T polymorphisms and colorectal cancer risk in a Chinese population.Methods
The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations.Results
The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR = 2.02, 95% CI = 1.55–2.57; TT: adjusted OR = 2.51, 95% CI = 1.82–3.47), compared with the CC genotype. Moreover, NQO1 609C > T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk.Conclusion
Our findings suggest that the NQO1 609C > T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking. 相似文献19.
Mingyi Ju Aoshuang Qi Jia Bi Lan Zhao Longyang Jiang Qiang Zhang Qian Wei Qiutong Guan Xueping Li Lin Wang Minjie Wei Lin Zhao 《Journal of cellular and molecular medicine》2020,24(11):6283-6297
High mortality of patients with cervical cancer (CC) stresses the imperative of prognostic biomarkers for CC patients. Additionally, the vital status of post-translational modifications (PTMs) in the progression of cancers has been reported by numerous researches. Therefore, the purpose of this research was to dig a prognostic signature correlated with PTMs for CC. We built a five-mRNA (GALNTL6, ARSE, DPAGT1, GANAB and FURIN) prognostic signature associated with PTMs to predict both disease-free survival (DFS) (hazard ratio [HR] = 3.967, 95% CI = 1.985-7.927; P < .001) and overall survival (HR = 2.092, 95% CI = 1.138-3.847; P = .018) for CC using data from The Cancer Genome Atlas database. Then, the robustness of the signature was validated using GSE44001 and the Human Protein Atlas (HPA) database. CIBERSORT algorithm analysis displayed that activated CD4 memory T cell was also an independent indicator for DFS (HR = 0.426, 95% CI = 0.186-0.978; P = .044) which could add additional prognostic value to the signature. Collectively, the PTM-related signature and activated CD4 memory T cell can provide new avenues for the prognostic predication of CC. These findings give further insights into effective treatment strategies for CC, providing opportunities for further experimental and clinical validations. 相似文献
20.
Umar M Upadhyay R Khurana R Kumar S Ghoshal UC Mittal B 《Molecular biology reports》2012,39(2):1153-1162
Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA
repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy
controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16–2.60, P = 0.007) in an allele dose-dependent manner (Ptrend = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18–2.67,
P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18–2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04–3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary,
p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population. 相似文献