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1.
Wan Zhao Lingmin Hu Jiali Xu Hongbing Shen Zhibin Hu Hongxia Ma Yongqian Shu Yongfeng Shao Yongmei Yin 《Cancer chemotherapy and pharmacology》2013,71(5):1287-1295
Purpose
Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy.Methods
We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy.Results
Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11–5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02–3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12–0.92).Conclusions
We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy. 相似文献2.
Qian Li Qing Lan Yawei Zhang Bryan A. Bassig Theodore R. Holford Brian Leaderer Peter Boyle Yong Zhu Qin Qin Stephen Chanock Nathaniel Rothman Tongzhang Zheng 《Cancer causes & control : CCC》2013,24(10):1875-1884
Purpose
Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene–nutrient interactions and the risk of non-Hodgkin lymphoma (NHL).Methods
We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene–nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000.Results
A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95 % CI 0.31–0.84), the homozygous CC genotype in MBD2 (rs603097, ?2176C>T) (OR = 0.37, 95 % CI 0.17–0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95 % CI 0.55–0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95 % CI 0.05–1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10?40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes.Conclusion
Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through gene–nutrient interactions involving dietary nutrient intakes. 相似文献3.
Moon Ju Jang Jong Woo Kim Young Joo Jeon So Young Chong Doyeun Oh Nam Keun Kim 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(6):1032-1041
Background
Angiogenesis plays an important role in tumor development, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. However, the contribution of common VEGF polymorphisms to colorectal cancer (CRC) prognosis remains unclear.Methods
We have genotyped four polymorphisms of VEGF (?2578C>A, ?1154G>A, ?634G>C, and 936C>T) in 350 CRC cases from the Korean population. The genotyping of VEGF polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay.Results
Although not every VEGF polymorphism was significantly correlated with patient prognosis in overall 350 CRC patients, we found that the VEGF ?2578CA genotype was associated with a significantly poor prognosis for rectal cancers compared to the CC genotype (HR = 2.156; 95 % CI 1.090–4.267; P = 0.028). In addition, we found that the ?2578A/?1154G/?634G/+936C haplotype was significantly associated with a decreased overall survival (OS) rate in all 350 CRC patients (HR = 2.530; 95 % CI 1.340–4.780; P = 0.004). In combination analysis, we found that the combined VEGF ?2578CA+AA/?1154GG genotype was associated with a poor OS rate in all 350 CRC patients (HR = 2.068; 95 % CI 1.159–3.693; P = 0.015).Conclusions
The VEGF gene polymorphisms investigated in this study were not found to be independent prognostic markers in Korean CRC populations. However, our results suggest that the VEGF ?2578C>A variant may be a potential genetic marker for rectal cancer prognosis. Further large population studies are warranted to define whether the ?2578C>A polymorphism is a prognostic marker of rectal cancer. 相似文献4.
Xie FJ Zhao P Kou JY Hong W Fu L Hu L Hong D Su D Gao Y Zhang YP 《Cancer chemotherapy and pharmacology》2012,69(6):1443-1448
Purpose
The GNAS1 gene is linked to proapoptotic signaling and correlates closely with clinical outcomes in many human cancers. The aim of this study was to evaluate whether the T393C polymorphism of the GNAS1 gene could be used as a chemotherapy sensitivity and prognosis predictive marker of advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum (GP).Methods
In this study, we performed the PCR-restriction fragment length polymorphism assay to examine the genotypes of the GNAS1 T393C polymorphism in 131 peripheral blood DNA specimens from advanced NSCLC patients with GP treatment.Results
The frequencies of the CC, CT, and TT genotypes in 131 advanced NSCLC cases were 25.2, 47.4, and 26.7%, respectively. The favorable TT genotype was significantly correlated with better overall survival (OS; P?0.05) and longer progress-free survival (PFS; P?0.05) compared with the CT or CC genotype. In the multivariate Cox proportional hazards model, the GNAS1 T393C polymorphism was independently associated with overall survival after adjusting the clinicopathological factors (P?0.05).Conclusions
This study suggests that the TT genotype of the GNAS1 T393C polymorphism could be an independent prognostic marker to predict chemotherapy sensitivity, favorable OS and PFS in advanced NSCLC patients with GP treatment. 相似文献5.
R. Mlak P. Krawczyk M. Ciesielka P. Kozioł I. Homa T. Powrózek M. Prendecka J. Milanowski T. Małecka-Massalska 《Clinical & translational oncology》2016,18(9):915-924
Purpose
Chemotherapy with platinum compounds and gemcitabine is frequently used in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients in which tyrosine kinase inhibitors (EGFR or ALK) cannot be administered. Unfortunately, less than half of the patients achieve the benefit from chemotherapy. Gemcitabine is an analog of deoxycytidine (pyrimidine antimetabolite) with antitumor activity. The excess of deoxycytidine synthesized by RRM1 enzyme activity may be a cause of competitive displacement of gemcitabine, which reduces the efficacy of this cytostatic. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of the RRM1 promoter (?37C>A, ?524C>T) and the effectiveness of first-line chemotherapy based on platinum compounds and gemcitabine in NSCLC patients.Patients and methods
SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 91 NSCLC patients.Results
The median progression-free survival (PFS) was significantly longer in carriers of AA (?37C>A) as well as CC (?524C>T) genotype of RRM1 compared to patients with other genotypes (10.5 vs 3.5 months, p = 0.0437; HR = 2.17, 95 % CI 1.02–4.62 and 10.5 vs 3.5 months, p = 0.0343; HR = 2.12, 95 % CI 1.06–4.27). In addition, the CC genotype carriers (?37C>A) showed a significant increase in the risk of shortening overall survival (OS) in comparison to patients with AA or AC genotypes (9.5 vs 18 months, p = 0.0193; HR = 2.13, 95 % CI 1.13–4.03).Conclusions
Presence of rare AA (?37C>A) and CC (?524C>T) genotypes of the RRM1 may be favorable predictive factors for chemotherapy with platinum compounds and gemcitabine in NSCLC patients.6.
Ning Sun Xinchen Sun Baoan Chen Hongyan Cheng Jifeng Feng Lu Cheng Zuhong Lu 《Cancer chemotherapy and pharmacology》2010,65(3):437-446
Purpose
The level of drug metabolism and drug transport is correlated with the sensitivity of cancer cells towards platinum-based chemotherapy. We hypothesize that genetic polymorphisms in metabolising enzymes gene GSTP1 (glutathione S-transferase P1), and MRP2 (multidrug resistance-associated protein 2) (ABCC2), which result in inter-individual differences in metabolism and drug disposition, may predict clinical response to platinum agents in advanced non-small cell lung cancer (NSCLC) patients.Methods
Totally 113 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and clinical response was evaluated after four cycles. MRP2 C-24T (?24C>T), MRP2 Val417Ile (1249G>A), MRP2 Ile1324Ile (3972C>T), and GSTP1 Ile105Val (342A>G) genotype were determined by gene-chip method (a 3-D (three dimensions) polyacrylamide gel-based DNA microarray method) using DNA samples isolated from peripheral blood collected before treatment. Pearson Chi-square test and Fisher’s exact test were performed to measure the differences of the chemotherapeutic efficacy among variant genotype. The odds ratios and 95% confidence intervals were computed by logistic regression.Results
The C→T change of MRP2 C-24T and the A→G change of GSTP1 Ile105Val polymorphism significantly increased platinum-based chemotherapy response.Conclusion
The polymorphic status of MRP2 C-24T and GSTP1 Ile105Val might be the predictive markers for the treatment response of advanced NSCLC patients. The DNA microarray-based method is accurate, high throughput and inexpensive, suitable for single-nucleotide polymorphism genotyping in a large number of individuals. 相似文献7.
An SJ Huang YS Chen ZH Su J Yang Y Chen JG Yan HH Lin QX Yang JJ Yang XN Zhou Q Zhang XC Wu YL 《Medical oncology (Northwood, London, England)》2012,29(2):627-632
We sought to find blood-based biomarkers that can be used to predict efficacy in advanced non-small cell lung cancer patients treated with bevacizumab plus chemotherapy. Blood was collected before treatment and after 6?weeks of therapy from patients who were participating in a phase 4 trial. Plasma vascular endothelial growth factor (VEGF) levels were evaluated by ELISA. A total of eight single nucleotide polymorphisms in four candidate genes were analyzed by PCR and sequencing. A total of 45 patients enrolled in a clinical trial at Guangdong General Hospital between August 2007 and March 2008 were used as subjects. The median survival times of OS was 25.6 and 13.4?months in the low and high groups, respectively, when the median posttreatment plasma VEGF level (46.63?pg/ml) was used as the cut-off point (P?=?0.0284). Patients carrying the AA genotype at the ?6C?>?A polymorphism in laminin 5 (LN5) were more likely to exhibit reduced hemoglobin compared with patients carrying the CA/CC genotype (OR?=?8.364, ??2?=?5.34, P?=?0.021). Similar associations were found at the ?89A?>?G and ?260C?>?A polymorphisms in LN5. Patients with the CC genotype at the ?6C?>?A polymorphism in LN5 had an increased risk of neutropenia than those with the CA/AA genotype (OR?=?4.444, ??2?=?5.116, P?=?0.030). Our results show improved survival in patients with lower posttreatment plasma VEGF levels treated with bevacizumab plus chemotherapy; thus, the posttreatment plasma VEGF level may be a promising biomarker to predict clinical benefit early in the course of therapy. Polymorphisms in LN5 were associated with a reduced level of hemoglobin and neutropenia. 相似文献
8.
Emmanouil Liamarkopoulos Maria Gazouli Gerasimos Aravantinos Nikolaos Tzanakis George Theodoropoulos Spyros Rizos Nikolaos Nikiteas 《Gastric cancer》2011,14(4):317-321
Background
Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association of CASP8 and CASP9 gene polymorphisms with gastric cancer (GC) susceptibility.Methods
We undertook a case?Ccontrol study of 88 GC cases and 480 controls to investigate the association between CASP8 ?652 6N ins/del and CASP9 ?1263 A>G polymorphisms and GC susceptibility by a polymerase chain reaction (PCR)-restriction fragment length polymorphism method.Results
CASP8 ?652 6N ins/del polymorphism and CASP9 ?1263 GG genotype were observed to be significantly associated with a reduced risk of GC. No significant association was observed between CASP8 ?652 6N ins/del and CASP9 ?1263 A>G polymorphisms and tumor characteristics. However, both CASP8 del/del and CASP9 ?1263 GG genotypes were associated with increased overall survival in GC patients.Conclusions
The CASP8 ?652 6N ins/del and the CASP9 ?1263 A>G polymorphisms were observed to play a protective role in GC predisposition. 相似文献9.
Narita S Tsuchiya N Yuasa T Maita S Obara T Numakura K Tsuruta H Saito M Inoue T Horikawa Y Satoh S Habuchi T 《International journal of clinical oncology / Japan Society of Clinical Oncology》2012,17(3):204-211
Objectives
Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC.Methods
Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60?mg/m2 on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560?mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed.Results
Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8?months, and the median total time of chemotherapy holiday was 7.7?months (range 1.7?C35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p?=?0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC?+?CT genotype (p?=?0.036).Conclusion
Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC. 相似文献10.
Chih-Ching Yeh Ching-Yu Lai Shih-Ni Chang Ling-Ling Hsieh Reiping Tang Fung-Chang Sung Yi-Kuei Lin 《International journal of clinical oncology / Japan Society of Clinical Oncology》2017,22(3):484-493
Background
This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan.Methods
We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan–Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival.Results
Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60–0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35–2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55–0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08–2.18).Conclusions
Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.11.
Xu Liang Jie Zhang Yulin Zhu Yuanli Lu Xinna Zhou Zheng Wang Jing Yu Ying Yan Lijun Di Li Che Hanfang Jiang Bin Shao Xiaoli Wang Huabing Yang Herbert Kim Lyerly Jun Ren 《Clinical & translational oncology》2013,15(4):331-334
Aim
This study was designed to explore the genetic polymorphism of IL-10 (?1082A/G, ?592A/C, ?819T/C), TNF-α (?308G/A) with susceptibility to docetaxel-induced liver injury (DILI) in Chinese breast cancer patients.Methods
The targeted genetic polymorphisms of IL10-1082G/A, IL10-592A/C, IL10-819T/C, TNF-308G/A from 40 patients with DILI were assayed by matrix-assisted laser desorption/ionization-time of flight of Sequenom.Results
AA genotype of IL10-592 and TT of IL10-819 significantly increased incidence of DILI (P = 0.005, OR = 3.137). No differences of TNF gene polymorphism between the two groups were seen.Conclusion
The genetic polymorphism of the IL10-592A/C AA genotype and IL10-819T/C TT genotype was predominantly conferred to the incidence of docetaxel-induced liver injury. 相似文献12.
Metro G Chiari R Mare M Giannarelli D Tofanetti FR Minotti V Ferraldeschi M Giuffrida D Marcomigni L Bennati C Fischer MJ Meacci M Bellavita R Pistola L Ludovini V Crinò L 《Cancer chemotherapy and pharmacology》2011,68(6):1405-1412
Purpose
In the present study, the combination of carboplatin (CBDCA) plus pemetrexed (PMX) for the treatment of patients with platinum-pretreated, pemetrexed-na?ve, advanced non-small cell lung cancer (NSCLC) was investigated. Also, single nucleotide polymorphisms (SNPs) at the XRCC3, XPD, ERCC1, GARFT, DHFR, and TS genes were investigated.Methods
Eighty patients treated with CBDCA/PMX at two Italian institutions were evaluable. Of these, 73 patients had blood samples collected for pharmacogenetic evaluation.Results
Overall, the median age was 59?years (26?C78), 59 patients (73.7%) had a performance status of 0, and 34 patients (42.5%) had stage IIIB disease. Thirty-eight patients (47.5%) had responded to prior first-line platinum-based therapy. Study treatment resulted into one complete and 33 partial responses for an overall response rate of 42.5%. The disease control rate was 77.5%. The median progression-free survival (PFS) and overall survival (OS) were 5.8?and 17.4?months, respectively. Responders achieved a significant longer PFS and OS versus non-responders (P?=?0.007 and P?=?0.003, respectively). The only grade 3?C4 adverse event occurring in more than 5.0% of patients was neutropenia (6 patients, 7.5%). No statistically significant association was noted between polymorphisms of the genes analyzed and clinical outcome.Conclusions
In patients with platinum-pretreated, advanced NSCLC and favorable clinical prognostic factors, treatment with CBDCA/PMX is associated with a good clinical outcome and toxicity profile. None of the SNPs analyzed was found to be a useful predictor of treatment efficacy. 相似文献13.
Cassio Cardoso-Filho Luis Otavio Sarian Camila Borges Martins de Oliveira Leonardo da Silveira Bossi Gustavo Jacob Lourenço Carmen Silvia Passos Lima Maria Salete Costa Gurgel 《Cancer chemotherapy and pharmacology》2013,72(3):529-535
Purpose
Individual differences in cytochrome P-450 efficiency partly explain their variations in resistance to tamoxifen and estrogen metabolism. Two polymorphisms of the CYP1A1 gene—A4889G and T6235C—are known to affect activation of estrone and estradiol and to deregulate concentration of highly active tamoxifen metabolites. However, the clinicopathologic implications of these findings have not yet been evaluated.Objective
The objective of this study is to evaluate whether T6235C and A4889G gene polymorphisms are related to pathological presentations and clinical outcomes of ER+/PR+ breast cancer (BC) in women using tamoxifen.Methods
We included 405 women with ER+/PR+ tumors, who used tamoxifen as their primary therapy, and for whom 5-year follow-up data were available. We evaluated associations within clinicopathologic features, including overall 5-year survival, with CYP1A1 gene status.Results
Univariate analysis showed that a slightly higher proportion of women with AG/GG genotypes were of European descent (P = 0.05) and that TC/CC genotype was significantly associated with premenopausal status (P = 0.01); however, no significant association remained after multivariate adjustment. Women with CYP1A1 genotypes other than AA and TT were more prone to develop low-grade tumors; 85.9 % of tumors in AA and TT genotype groups were grade III, but only 76.1 % of tumors in carriers of the polymorphisms were grade III (adjusted P = 0.02; OR 0.51 for grade III disease; 95 % CI 0.28–0.93). After 60 months of follow-up, ~75 % of the women were alive. There was no significant difference in survival related to the CYP1A1 gene status.Conclusions
Breast cancer patients carrying CYP1A1 gene polymorphisms developed less aggressive tumors, but showed no evidence of better prognoses. 相似文献14.
Kiran Lata Sharma Meenakshi Umar Manmohan Pandey Sanjeev Misra Ashok Kumar Vijay Kumar Balraj Mittal 《Journal of gastrointestinal cancer》2013,44(4):436-443
Background and Objectives
Phospholipase C epsilon 1 (PLCE1) plays crucial roles in carcinogenesis and progression of esophageal and gastric cancers. In the present study, we investigated association of GWAS identified rs2274223 A>G and. rs7922612 T>C polymorphism of PLCE1 with susceptibility to gallbladder cancer (GBC).Methods
The study involved genotyping of selected PLCE1 variants in 416 GBC cases and 225 controls. Haplotype analysis was done by SNPStats. In silico analyses were performed using bioinformatic tools.Results
PLCE1 rs2274223 [AG] and rs7922612 [CC] genotypes were found to be significantly associated with an increased risk of GBC [OR?=?1.9, p?=?0.002; OR?=?2.0, p?=?0.04, respectively]. PLCE1 haplotype [Grs2274223-Crs7922612] also showed significant association with GBC [OR?=?1.8, p?=?0.04]. The association was significant in females and GBC patients with stones and female GBC patients with gallstones [OR?=?2.6, p?=?0.01; OR?=?3.3, p?=?0.007], respectively. However, no significant associations with other risk factors such as tobacco usage and age of onset were found. Functional prediction of rs2274223 A>G suggested change in protein coding and splicing regulation.Conclusion
The present study found a significant association of PLCE1 rs2274223 and rs7922612 polymorphisms with susceptibility to GBC probably through gallstone-mediated inflammatory pathway. 相似文献15.
Liwen Xiong Jinsong Cheng Jinyu Gao Jipeng Wang Xiaoning Liu Lixin Wang 《Clinical lung cancer》2013,14(4):433-439
BackgroundThe aim of this study was to explore the association between vitamin D receptor (VDR) genetic polymorphisms and platinum-based chemotherapy response as well as the prognosis of non–small-cell lung cancer (NSCLC) in a Chinese cohort.Patients and MethodsSeven hundred fifty-five patients with advanced NSCLC (stage III [A + B] or stage IV) were enrolled. Platinum-based chemotherapy was given to each patient with NSCLC, and the therapeutic effect was evaluated. The VDR polymorphisms were genotyped.ResultsThree hundred twenty-one (42.5%) patients responded to chemotherapy (complete response [CR] or partial response [PR]) and 434 (57.5%) patients were nonresponders (stable disease [SD] or progressive disease [PD]). The genotypic and allelic frequencies of FokI, BsmI, and TaqI were not significantly different between chemotherapy responders and nonresponders. However, the genotypic and allelic frequencies of ApaI thymine (T) > guanine (G) were significantly different between the responders and nonresponders. Multivariate logistic regression analysis showed that GG genotype carriers of ApaI T > G had a higher chance of being responders. The ApaI T > G polymorphisms affected mean overall survival (OS). The GG genotype carriers of ApaI polymorphisms had a longer mean OS compared with TT carriers. Multivariate Cox regression analyses showed that ApaI T > G was significantly associated with OS.ConclusionWe found that there was an effect of ApaI T > G polymorphisms of the VDR gene on the chemotherapy response in patients with NSCLC, as well as a prognostic role of the VDR gene polymorphisms in Chinese patients with advanced NSCLC. 相似文献
16.
Yee Soo Chae Jong Gwang Kim Sang Kyun Sohn Joon Ho Moon Shi Nae Kim Su Jeong Lee Tae-In Park Myung-Hoon Lee 《Cancer chemotherapy and pharmacology》2010,65(3):571-577
Purpose
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease entity due to diverse clinical outcomes to treatment. Most anticancer agents, regardless of their distinct mechanisms of action, ultimately kill cancer cells by inducing apoptosis. Accordingly, the present study analyzed the impact of polymorphisms of apoptosis-related genes on outcome in DLBCL patient treated with R-CHOP.Patients and methods
Ninety patients with DLBCL treated with R-CHOP were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and 22 polymorphisms of 18 apoptosis-related genes were assessed using a polymerase chain reaction–restriction fragment length polymorphism assay.Results
All the evaluable patients were responsive to R-CHOP. The multivariate analysis showed that the AA genotype of lymphotoxin alpha (LTA) C804A (rs1041981) and GG genotype of RIPK1 G83A (rs2272990) were significantly correlated with a worse time to progression (TTP) compared with the combined C/A and C/C genotype and the combined G/A and A/A genotype (hazard ratio [HR] = 7.92; 95% confidence interval [CI] = 1.42–44.18; P = 0.018 and HR = 20.02; 95% CI = 1.59–251.52; P value = 0.018, respectively), whereas no association was observed between the other polymorphisms and TTP.Conclusion
The polymorphisms of LTA (rs1041981) and RIPK1 (rs2272990) may correlate with TTP in patients with DLBCL treated with R-CHOP. 相似文献17.
X.-P. Guo Y. Wang H. Zhao S.-D. Song J. Zhou Y. Han 《Clinical & translational oncology》2014,16(7):623-629
Objectives
To investigate the relationship of the MTHFR polymorphisms (C677T) and the risk of CRC by meta-analysis.Methods
Relevant literatures concerning the association between the MTHFR C677T polymorphism and the risk of CRC were searched using the electronic database PubMed, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI). Odds ratio (ORs) and 95 % confidence intervals (CIs) were determined to assess the gene–disease association using fixed or random effect models, according to the heterogeneity among included studies.Results
The study shows that the MTHFR 677 TT homozygous genotype significantly decreases the risk of CRC in Asians (TT vs. CC: OR = 0.82, 95 % CI 0.73–0.92; TT vs. CT: OR = 0.84, 95 % CI 0.75–0.94; TT vs. CC+TT: OR = 0.83, 95 % CI 0.75–0.93).Conclusion
This meta-analysis indicated that the MTHFR 677 TT homozygous genotype decreased the risk of CRC in Asians, while the MTHFR 677 CT heterozygous genotype did not contribute to CRC susceptibility. 相似文献18.
Cui Chen Fenghua Wang Zhiqiang Wang Cong Li Huiyan Luo Ying Liang Xin An Jianyong Shao Yuhong Li 《Cancer chemotherapy and pharmacology》2013,72(2):315-322
Objectives
We evaluated whether DNA repair gene polymorphisms had an effect on clinical outcomes in metastatic/recurrent nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based chemotherapy.Materials and methods
Clinical data of 101 patients with metastatic/recurrent NPC between 2004 and 2011 were reviewed. Five potentially functional polymorphisms (ERCC1 Asn118Asn, ERCC1 C8092A, XPD Lys751Gln, XRCC1 Arg399Gln and XRCC1 Arg280His) were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Results
The ERCC1 C8092A polymorphism was an independent predictor of PFS in Chinese NPC patients treated with cisplatin-based chemotherapy. Compared to the patients carrying the C/C genotype, the patients with the C/A or A/A genotype had an increased risk of disease progression on cisplatin-based chemotherapy (7.9 vs. 9.3 months; HR 1.61; 95 % CI 1.08–2.61; p = 0.047). However, no association between the other polymorphisms, response rate, disease progression and survival was detected in metastatic/recurrent NPC patients.Conclusion
The ERCC1 C8092A polymorphism might be a useful predictive marker in metastatic/recurrent NPC patients treated with cisplatin-based chemotherapy. However, a large-scale prospective study is warranted to validate our findings. 相似文献19.
S. Zidi Y. Ben Othmen E. Ghazouani A. Mezlini A. Lagha B. Slimen M. Afrit B. Yacoubi Loueslati 《Journal africain du cancer / African Journal of Cancer》2013,5(3):162-168
Objective
We assessed the polymorphism G>A at position 308 of the promoter of the gene encoding the TNF-α as a risk factor for cervical cancer in Tunisia. We also investigated whether this polymorphism is associated with histological type and/or FIGO stage of cervical tumor.Materials and methods
Polymorphism G>A at position 308 of the promoter of the gene encoding the TNF-α is analyzed by ARMS-PCR in 103 Tunisian patients with cervical cancer and 138 healthy Tunisian women. The search for associations between this polymorphism and cervical cancer is based on the χ2 test or Fisher’s exact test.Results
The G allele is more frequent than the A allele in patients (63.11%) and healthy controls (65.58%). The heterozygous genotype GA is the most represented with a frequency of 56.31% in patients and 52.90% in controls. Homozygous genotypes GG and AA were found respectively at 34.95 and 8.74% patients and 39.13 and 7.97% healthy controls. Comparing the distribution of genotype frequencies between patients and healthy controls revealed no significant differences neither between allele A (AA + GA vs. GG) and the rest (p = 0.5070), nor between the G allele (GG vs. GA + AA) and the rest (p = 0.8309).Conclusion
The ?308 G/A polymorphism of TNF-α gene promoter is not associated with cervical cancer or the stage and histological type of cervical tumor in Tunisia. 相似文献20.
Xue-Ning Yang Ling Huang Yu Chen She-Juan An Xu-Chao Zhang Ri-Qiang Liao Jian Su Yi-Long Wu 《中国癌症研究》2015,27(3):301-308