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1.  Oxidative Stress-Related Genetic Polymorphisms Are Associated with the Prognosis of Metastatic Gastric Cancer Patients Treated with Epirubicin, Oxaliplatin and 5-Fluorouracil Combination Chemotherapy 
PLoS ONE  2014;9(12):e116027.
Background
Oxidative stress genes are related to cancer development and treatment response. In this study, we aimed to determine the predictive and prognostic roles of oxidative stress-related genetic polymorphisms in metastatic gastric cancer (MGC) patients treated with chemotherapy.
Methods
In this retrospective study, we genotyped nine oxidative stress-related single nucleotide polymorphisms (SNPs) in NQO1, SOD2, SOD3, PON1, GSTP1, GSTT1, and NOS3 (rs1800566, rs10517, rs4880, rs1799895, rs662, rs854560, rs1695, rs2266637, rs1799983, respectively) in 108 consecutive MGC patients treated with epirubicin, oxaliplatin, and 5-fluorouracil (EOF) regimen as the first-line chemotherapy and analyzed the association between the genotypes and the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Results
We found that, in addition to a lower pathological grade (p = 0.017), NQO1 rs1800566 CT/TT genotype was an independent predictive factor of poor PFS (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.23–3.16; p = 0.005). PON1 rs662 AA/AG genotype was significantly associated with poor OS (HR = 1.95, 95% CI = 1.07–3.54; p = 0.029). No associations were detected between the nine SNPs and DCR.
Conclusions
NQO1 rs1800566 is an independent predictive factor of PFS for MGC patients treated with EOF chemotherapy, and PON1 rs662 is a noteworthy prognostic factor of OS. Information on oxidative stress-related genetic variants may facilitate optimization of individualized chemotherapy in clinical practice.
doi:10.1371/journal.pone.0116027
PMCID: PMC4278770  PMID: 25545243
2.  Pri-miR-124 rs531564 and pri-miR-34b/c rs4938723 Polymorphisms Are Associated with Decreased Risk of Esophageal Squamous Cell Carcinoma in Chinese Populations 
PLoS ONE  2014;9(6):e100055.
MicroRNAs are a new class of small non-protein-coding RNAs that sometimes function as tumor suppressors or oncogenes. Aberrant expression and structural alteration of microRNAs have been reported to be involved in tumorigenesis and cancer development. Recently, rs531564/pri-miR-124-1, rs4938723/pri-miR-34b/c, rs7372209/pri-miR-26a-1, rs895819/pre-miR-27a, and rs11134527/pri-miR-218 were reported to be associated with risks of various cancers. In order to evaluate the relationship of these SNPs and esophageal squamous cell carcinoma (ESCC) risk, we conducted a case-control study with 1109 ESCC patients and 1275 control subjects to examine the potential association of these pri/pre-miRNA polymorphisms with ESCC susceptibility. As a result, two SNPs were associated with a significant risk of ESCC. We found that the GG genotype of pri-miR-124-1 rs531564 was associated to a significantly decreased risk of ESCC comparing with the CC/CG genotypes (p = 0.005; OR = 0.61, 95% CI = 0.43–0.86). In addition, the CC genotype of pri-miR-34b/c rs4938723 was associated with a significant decreased risk of ESCC (CC VS. TT/TC: p = 0.007, OR = 0.82, 95% CI = 0.71–0.95) in Chinese population. The present study provides the first evidence that pri-miR-124-1 rs531564 and pri-miR-34 rs4938723 were associated with the risk of ESCC in Chinese population.
doi:10.1371/journal.pone.0100055
PMCID: PMC4063769  PMID: 24945256
3.  Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer 
Although nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is approved to be given every 3 weeks, weekly use of this drug is becoming a new standard of care in patients with metastatic breast cancer (MBC). This prospective Phase II study was conducted to improve the efficacy of weekly nab-paclitaxel with cisplatin in MBC patients. Seventy-three women with recurrent or MBC were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m2 on day 1, day 8, and day 15, followed by cisplatin 75 mg/m2 on day 1, repeated every 28 days with a maximum of 6 cycles. The primary objective was investigator-assessed overall response rate (ORR). A high ORR of 67.1% was obtained, with rates of 80.6% for the first-line patients and 80% for patients not pretreated with taxanes. Among those who had objective responses, a large percentage of patients (83.7%) showed quickly remarkable tumor shrinkage during the first two cycles. The median progression-free and overall survival times were 9.8 and 26.9 months, respectively. For the patients receiving first-, second-, and third-line therapy or beyond, median progression-free survival was 11.7, 7.7, and 7.6 months, respectively (P=0.005). Molecular subtype was not significantly associated with ORR or disease progression. Grade 4 neutropenia occurred in 46 patients (63.0%), with febrile neutropenia found in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%). Efficacy of weekly nab-paclitaxel can be improved by adding cisplatin. The doublet is highly effective, with quick response, manageable toxicity, and possible equivalence across molecular subtypes in MBC patients.
doi:10.2147/IJN.S58275
PMCID: PMC3964033  PMID: 24672237
metastatic breast cancer; nanoparticle albumin-bound paclitaxel; cisplatin; taxane-pretreated
4.  Potentially Functional Variants of PLCE1 Identified by GWASs Contribute to Gastric Adenocarcinoma Susceptibility in an Eastern Chinese Population 
PLoS ONE  2012;7(3):e31932.
Background
Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls.
Methodology/Principal Findings
We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14–1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05–1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (Ptrend = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05).
Conclusions/Significances
Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.
doi:10.1371/journal.pone.0031932
PMCID: PMC3295761  PMID: 22412849
5.  The FAS ligand promoter polymorphism, rs763110 (−844C>T), contributes to cancer susceptibility: evidence from 19 case–control studies 
European Journal of Human Genetics  2009;17(10):1294-1303.
The potentially functional polymorphism, rs763110 (−844C>T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11 105 cancer cases and 11 372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR=0.80, 95% CI: 0.68–0.95, Pheterogeneity=0.001; heterozygote comparison: OR=0.82, 95% CI: 0.72–0.95, Pheterogeneity<0.001; dominant model comparison: OR=0.82, 95% CI: 0.71–0.94, Pheterogeneity<0.001; and recessive model comparison: OR=0.88, 95% CI: 0.81–0.96, Pheterogeneity=0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk.
doi:10.1038/ejhg.2009.45
PMCID: PMC2986648  PMID: 19337311
FAS ligand; polymorphism; cancer susceptibility; meta-analysis

Results 1-5 (5)