scholarly journals Impact of AKAP6 Polymorphisms on Glioma Susceptibility and Prognosis

2019 ◽  
Author(s):  
Ming Zhang ◽  
Yonglin Zhao ◽  
Junjie Zhao ◽  
Tingqin Huang ◽  
Xiaoye Guo ◽  
...  

Abstract Purpose Glioma is the most common primary malignant brain tumor with high mortality and poor prognosis. Our aim was to clarify the correlation between AKAP6 gene polymorphisms and glioma susceptibility and prognosis in Chinese Han population. Methods Five single-nucleotide polymorphisms (SNPs) of AKAP6 were genotyped by Agena MassARRAY in 575 glioma patients and 500 healthy controls. Logistic regression model was utilized to calculate odds ratios (OR) and 95% confidence intervals (CI). The associations between polymorphisms and survival were assessed using the log-rank test, Kaplan-Meier analysis and Cox regression model. Results We found that rs2239647 polymorphism was strongly associated with an increased risk of glioma (OR = 1.90, p = 0.007) and a worse prognosis for glioma, especially in high-grade glioma (HR = 1.67, p = 0.034). Stratified analysis showed that rs2239647 increased the risk of glioma in female (OR = 1.62, p = 0.016). Whereas, rs4261436 (HR = 0.70, p = 0.045) and rs17522122 (HR = 0.75, p = 0.016) were associated with better prognosis of astrocytoma. In addition, we also found that surgical methods and chemotherapy are critical factors for the prognosis of glioma patients. Conclusions This study firstly provided evidence for the impact of AKAP6 polymorphisms on susceptibility and prognosis of glioma, suggesting AKAP6 variants might have potential roles in the etiology of glioma.

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ming Zhang ◽  
Yonglin Zhao ◽  
Junjie Zhao ◽  
Tingqin Huang ◽  
Yuan Wu

Abstract Purpose Glioma is the most common primary malignant brain tumor with high mortality and poor prognosis. Our aim was to clarify the correlation between Kinase-anchored protein 6 (AKAP6) gene polymorphisms and glioma susceptibility and prognosis in Chinese Han population. Methods Five single-nucleotide polymorphisms (SNPs) of AKAP6 were genotyped by Agena MassARRAY in 575 glioma patients and 500 healthy controls. Logistic regression model was utilized to calculate odds ratios (OR) and 95% confidence intervals (CI). The associations between polymorphisms and survival were assessed using the log-rank test, Kaplan-Meier analysis and Cox regression model. Results We found that rs2239647 polymorphism was strongly associated with an increased risk of glioma (OR = 1.90, p = 0.007) and a worse prognosis for glioma, especially in high-grade glioma (HR = 1.67, p = 0.034). Stratified analysis showed that rs2239647 increased the risk of glioma in female (OR = 1.62, p = 0.016). Whereas, rs4261436 (HR = 0.70, p = 0.045) and rs17522122 (HR = 0.75, p = 0.016) were associated with better prognosis of astrocytoma. In addition, we also found that surgical methods and chemotherapy are critical factors for the prognosis of glioma patients. Conclusions This study firstly provided evidence for the impact of AKAP6 polymorphisms on susceptibility and prognosis of glioma, suggesting AKAP6 variants might have potential roles in the etiology of glioma.


2019 ◽  
Author(s):  
Ming Zhang ◽  
Yonglin Zhao ◽  
Junjie Zhao ◽  
Tingqin Huang ◽  
Yuan Wu

Abstract Purpose Glioma is the most common primary malignant brain tumor with high mortality and poor prognosis. Our aim was to clarify the correlation between AKAP6 gene polymorphisms and glioma susceptibility and prognosis in Chinese Han population. Methods Five single-nucleotide polymorphisms (SNPs) of AKAP6 were genotyped by Agena MassARRAY in 575 glioma patients and 500 healthy controls. Logistic regression model was utilized to calculate odds ratios (OR) and 95% confidence intervals (CI). The associations between polymorphisms and survival were assessed using the log-rank test, Kaplan-Meier analysis and Cox regression model. Results We found that rs2239647 polymorphism was strongly associated with an increased risk of glioma (OR = 1.90, p = 0.007) and a worse prognosis for glioma, especially in high-grade glioma (HR = 1.67, p = 0.034). Stratified analysis showed that rs2239647 increased the risk of glioma in female (OR = 1.62, p = 0.016). Whereas, rs4261436 (HR = 0.70, p = 0.045) and rs17522122 (HR = 0.75, p = 0.016) were associated with better prognosis of astrocytoma. In addition, we also found that surgical methods and chemotherapy are critical factors for the prognosis of glioma patients. Conclusions This study firstly provided evidence for the impact of AKAP6 polymorphisms on susceptibility and prognosis of glioma, suggesting AKAP6 variants might have potential roles in the etiology of glioma.


2020 ◽  
Vol 14 (1) ◽  
pp. 13-22
Author(s):  
XiuLan Liu ◽  
Guangji Yang ◽  
Juan Huang ◽  
Li Chai ◽  
Xun Liu ◽  
...  

Aim: KRAS SNPs may increase KRAS transcription and KRAS levels. SNPs of KRAS 3′UTR can affect carcinoma risk and prognosis. Materials & methods: The rs8720 and rs7960917 in KRAS 3′UTR for colorectal carcinoma (CRC) risk and survival were investigated in a case–control study. Association between SNPs and CRC risk, survival analysis were analyzed by an unconditional logistic regression model, log-rank test, Kaplan–Meier estimation, Cox regression model and one-way analysis of variance. Results & conclusion: The genotype CT of rs8720 was significantly increased risk of CRC, decreased overall survival and event-free survival, and KRAS mRNA and protein expressions were significantly increased in individuals with rs8720 CT, TT genotype. rs8720 may be an important factor in CRC development and prognosis.


2019 ◽  
Author(s):  
Tuo Wang ◽  
Yao Sun ◽  
Zichao Xiong ◽  
Jiamin Wu ◽  
Xiaoying Ding ◽  
...  

Abstract BACKGROUND Glioma is the most frequent malignant primary brain tumor, and the outcomes for patients with glioma remain poor. The purpose of this study is to explore the association between ANXA6 polymorphisms and glioma risk as well as the prognosis of glioma patients in the Chinese Han population.METHODS We selected nine single-nucleotide polymorphisms (SNPs) in ANXA6 which were genotyped by Agena MassARRAY from 593 glioma patients and 589 healthy controls. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The association between polymorphisms and survival of glioma patient were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis. RESULTS: Overall analysis found that rs3762993 was significantly associated with an increased glioma risk. Stratification analysis found that rs11960458 was strongly associated with an increased risk of glioma in age >41; rs3762993 was also found to be associated an increased with glioma risk in age >41, ≤41, male and low-grade glioma; but rs4958892 was associated with a decreased risk of glioma in age>41 and male. Interestingly, rs11960458 and rs888988 were correlated with poor prognosis of glioma patient. Furthermore, age, extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients.CONCLUSIONS In conclusion, our results indicated that ANXA6 polymorphisms were associated with glioma susceptibility and prognosis. Further studies are required to confirm the results and elucidate the mechanisms of the ANXA6 polymorphisms affect the glioma risk and prognosis.


2020 ◽  
Author(s):  
Xiaoying Ding ◽  
Yaqin Zhao ◽  
Haozheng Yuan ◽  
Yong Zhang ◽  
Ya Gao

Abstract Background: Genetic factors play a crucial role in the glioma risk and prognosis of glioma patients. To explore the role of PVT1 polymorphism in the susceptibility and survival of glioma in the Chinese Han population, we conducted a case-control study.Methods: The three single-nucleotide polymorphisms (SNPs) in PVT1 were genotyped using Agena MassARRAY from 575 patients with glioma and 500 healthy controls. We used the χ 2 test to analyze the differences in distribution of allele and genotype between the cases and controls. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The effects of polymorphisms and clinical features on survival of glioma patients were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis.Results: We found that rs13255292 was associated with a decreased risk of glioma in the recessive model in overall or male; and rs4410871 was significantly associated with an increased the risk of glioma in age≤40 years old or female. Moreover, the extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients. However, the gender, age, tumor grade, radiotherapy and PVT1 polymorphisms have no effect on prognosis of glioma patients.Conclusions: Our results indicated that PVT1 polymorphisms (rs13255292 and rs4410871) were associated with glioma susceptibility, but have no effect on prognosis of glioma patients. Further studies with large samples are required to confirm the results.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Takaya Kitano ◽  
Tsutomu Sasaki ◽  
Yasufumi Gon ◽  
Kenichi Todo ◽  
Shuhei Okazaki ◽  
...  

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 584-584
Author(s):  
Weining Wang ◽  
Chin Jin Seo ◽  
Grace Hwei Ching Tan ◽  
Claramae Shulyn Chia ◽  
Khee Chee Soo ◽  
...  

584 Background: Right and left-sided colon cancers are embryonically distinct and present differently. Recently, there has been growing belief that sidedness could be independently associated with survival outcomes. This has important clinical implications regarding the prognostication, management and surveillance of colon cancer patients. Hence, we aim to investigate the impact of sidedness on survival in our patient population in this study. Methods: Patients who had primary treatment naïve colon cancer who underwent curative surgical resection in our institution from September 2002 to December 2010 were included in this study. Demographic and clinicopathological data was collected from electronic records and clinical charts. Tumours arising from the cecum, ascending colon, hepatic flexure and transverse colon were considered right-sided, while those arising from splenic flexure and descending colon were considered left-sided. Cancers of the rectosigmoid junction and rectum were excluded. Kaplan-Meier curves and log-rank test were used to compare overall, locoregional recurrence-free and distant recurrence-free survivals (OS, LRFS, DRFS respectively) between both groups. Multivariate analysis was performed using Cox regression proportional hazards. Results: 389 patients were included in this study. 238 had left-sided tumours while the remaining 151 had right-sided tumours. In our cohort, right-sided tumours were associated with older age and mucinous histology. Kaplan-Meier curves plotted showed improved LRFS in left-sided tumours (p = 0.04, median survival not reached) but no significant difference in OS and DRFS. On multivariate analysis, sidedness was also found to be an independent prognostic factor for LRFS but not OS and DRFS despite factoring in age, size of tumour, pT, pN and histology. Conclusions: Our study suggests that left-sided tumours in primary colon cancer are independently prognostic for improved locoregional survival as compared to the right-sided tumours, even after taking into account other known factors such as age, staging and histology.


2014 ◽  
Vol 120 (3) ◽  
pp. 716-724 ◽  
Author(s):  
Zhiyuan Xu ◽  
David Schlesinger ◽  
Krisztina Moldovan ◽  
Colin Przybylowski ◽  
Xingwen Sun ◽  
...  

Object The authors evaluate the impact of target location on the rate of pain relief (PR) in patients with intractable trigeminal neuralgia (TN) undergoing stereotactic radiosurgery (SRS). Methods The authors conducted a retrospective review of 99 patients with idiopathic TN who were identified from a prospectively maintained database and were treated with SRS targeting the dorsal root entry zone with a maximum dose of 80 Gy. Targeting of the more proximal portion of a trigeminal nerve with the 50% isodose line overlapping the brainstem was performed in 36 patients (proximal group). In a matched group, 63 patients received SRS targeting the 20% isodose line tangential to the emergence of the brainstem (distal group). The median follow-up time was 33 months (range 6–124 months). Results The actuarial rate of maintenance of Barrow Neurological Institute (BNI) Pain Score I–IIIa was attained in 89% of patients at 1 year, 81% at 2 years, and 69% at 4 years, respectively, after SRS. Kaplan-Meier analysis revealed that durability of PR was only associated with the proximal location of the radiosurgical target (log-rank test, p = 0.018). Radiosurgery-induced facial numbness (BNI Score II or III) developed in 35 patients, which was significantly more frequent in the proximal group (19 patients [53%] compared with 16 [25%] in the distal group [p = 0.015]). Conclusions The radiosurgical target appears to affect the duration of pain relief in patients with idiopathic trigeminal neuralgia with the target closer to the brainstem affording extended pain relief. However, the proximal SRS target was also associated with an increased risk of mild to moderate facial numbness.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S378-S379
Author(s):  
Guillermo Rodriguez-Nava ◽  
Goar Egoryan ◽  
Daniela Patricia Trelles-Garcia ◽  
Maria Adriana Yanez-Bello ◽  
Qishuo Zhang ◽  
...  

Abstract Background Growing evidence supports the use of remdesivir and tocilizumab for the treatment of hospitalized patients with severe COVID-19. The purpose of this study was to evaluate the use of remdesivir and tocilizumab for the treatment of severe COVID-19 in a community hospital setting. Methods We used a de-identified dataset of hospitalized adults with severe COVID-19 according to the National Institutes of Health definition (SpO2 < 94% on room air, a PaO2/FiO2 < 300 mm Hg, respiratory frequency > 30/min, or lung infiltrates > 50%) admitted to our community hospital located in Evanston Illinois, between March 1, 2020, and March 1, 2021. We performed a Cox proportional hazards regression model to examine the relationship between the use of remdesivir and tocilizumab and inpatient mortality. To minimize confounders, we adjusted for age, qSOFA score, noninvasive positive-pressure ventilation, invasive mechanical ventilation, and steroids, forcing these variables into the model. We implemented a sensitivity analysis calculating the E-value (with the lower confidence limit) for the obtained point estimates to assess the potential effect of unmeasured confounding. Figure 1. Kaplan–Meier survival curves for in-hospital death among patients treated with and without steroids The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 2. Kaplan–Meier survival curves for in-hospital death among patients treated with and without remdesivir The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Results A total of 549 patients were included. The median age was 69 years (interquartile range, 59 – 80 years), 333 (59.6%) were male, 231 were White (41.3%), and 235 (42%) were admitted from long-term care facilities. 394 (70.5%) received steroids, 192 (34.3%) received remdesivir, and 49 (8.8%) received tocilizumab. By the cutoff date for data analysis, 389 (69.6%) patients survived, and 170 (30.4%) had died. The bivariable Cox regression models showed decreased hazard of in-hospital death associated with the administration of steroids (Figure 1), remdesivir (Figure 2), and tocilizumab (Figure 3). This association persisted in the multivariable Cox regression controlling for other predictors (Figure 4). The E value for the multivariable Cox regression point estimates and the lower confidence intervals are shown in Table 1. Figure 3. Kaplan–Meier survival curves for in-hospital death among patients treated with and without tocilizumab The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 4. Forest plot on effect estimates and confidence intervals for treatments The hazard ratios were derived from a multivariable Cox regression model adjusting for age as a continuous variable, qSOFA score, noninvasive positive-pressure ventilation, and invasive mechanical ventilation. Table 1. Sensitivity analysis of unmeasured confounding using E-values CI, confidence interval. Point estimate from multivariable Cox regression model. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully: i.e., a confounder not included in the multivariable Cox regression model associated with remdesivir or tocilizumab use and in-hospital death in patients with severe COVID-19 by a hazard ratio of 1.64-fold or 1.54-fold each, respectively, could explain away the lower confidence limit, but weaker confounding could not. Conclusion For patients with severe COVID-19 admitted to our community hospital, the use of steroids, remdesivir, and tocilizumab were significantly associated with a slower progression to in-hospital death while controlling for other predictors included in the models. Disclosures All Authors: No reported disclosures


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5022-5022
Author(s):  
E. C. de Haas ◽  
N. Zwart ◽  
C. Meijer ◽  
H. M. Boezen ◽  
G. van der Steege ◽  
...  

5022 Background: With bleomycin, etoposide and cisplatin, cure of disseminated TC exceeds 80%. Next to tumor characteristics, response to chemotherapy may be determined by polymorphisms of genes involved in metabolism or target pathways of cytotoxic drugs. We investigated whether the A1450G polymorphic site in the gene for BLMH, an enzyme that inactivates bleomycin, is associated with differences in survival. Methods: Data were collected on survival of non-seminomatous TC patients treated with bleomycin and platinum from 1977–2003. BLMH genotype was determined from genomic DNA by PCR + restriction fragment length polymorphism analysis. The 3 genotypes [AA (wild-type), AG (heterozygote variant) and GG (homozygote variant)] were compared for patient characteristics, prognostic factors and received chemotherapy (Mann-Whitney U or χ2 test) and survival (Kaplan-Meier + log-rank test and Cox regression). Results: Data on BLMH genotype and survival were available for 304/372 patients (82%) with median follow-up of 10 yrs (range 0–27). The 3 genotypes AA (n=140), AG (n=133) and GG (n=31) did not differ significantly with respect to age, IGCCC prognosis, creatinine clearance and received dose of bleomycin and platinum. Overall survival of the GG genotype (61%) was worse than the overall survival of AA and AG combined (83%) (p=0.004), due to worse TC related survival of GG (71%) compared to AA + AG (90%) (p=0.001). Homozygote variants (GG) had a significantly increased risk for TC related death (odds ratio (OR) = 4.97) compared to wildtypes (AA) ( table ). Conclusion: Germline presence of the homozygote variant (GG) of the BLMH gene appears to be an unfavorable prognostic factor for TC related death after chemotherapy, in addition to the commonly used IGCCC prognosis. It is unclear whether this is due to alterations in metabolism or target pathways of bleomycin or other cytotoxic agents, or linkage disequilibrium to a yet unknown involved gene. This needs to be unraveled in future research. [Table: see text] No significant financial relationships to disclose.


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