• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.701-705
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• 2013

Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the response to platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newly diagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147, rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction (PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatment response when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TT genotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, and the hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, we found a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotype when compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our study found that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-based chemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis.

• Genomics & Informatics
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• v.20 no.4
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• pp.42.1-42.11
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• 2022

Breast cancer (BC) is a significant threat to female health, with both modifiable and non-modifiable risk factors. It is essential to monitor patients regularly and to raise population awareness. Increasing research also suggests that E-selectin (SELE) may increase tumor angiogenesis and the development of cancer. This study investigated SELE single-nucleotide polymorphisms (SNPs) in the following positions: rs5367T/C, rs5368C/T, rs5362T/G, and rs5362T/C. Using polymerase chain reaction, significant differences in allele and genotype frequencies were found between BC patients and controls. Position rs5368 was associated with an increased risk of BC for the CT and TT genotypes, with odds ratios (ORs) of 16.3 and 6.90 (Fisher probability = 0.0001, p = 0.005). Women with the T allele had a 19.3-fold higher incidence of BC, while allele C may be a protective allele against BC (OR, 0.05). Heterozygous genotypes at rs5367, rs5362, and rs5362 were significantly more common in BC patients, with ORs of 5.70, 4.50, and 3.80, respectively. These SNPs may be associated with the risk of BC, because the frequency of mutant alleles was significantly higher in patients (OR: 4.26, 3.83, and 4.30, respectively) than in controls (OR: 0.23, 0.30, and 0.20, respectively). These SNPs may be considered a common genotype in the Iraqi population, with the wild-type allele having a protective fraction and the mutant allele having an environmental fraction. The results also revealed a 2-fold increase in gene expression in BC patients compared to controls, with a significant effect (p = 0.017). This study's findings confirm the importance of SELE polymorphisms in cancer risk prediction.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4985-4989
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• 2016

Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8083-8087
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• 2014

Purpose: To investigate the association of IL-17F rs763780T>C with cancer risk. Materials and Methods: We searched the Cochrane Central Library, PubMed, MEDLINE, EMBASE, CNKI (China National Knowledge Infrastructure) and WangFang databases until May 2014 for a meta-analysis conducted using RevMan 5.2 software. Results: A total of ten papers were included into this meta analysis, involving 3, 336 cases and 4, 217 healthy people. There were no significant differences on association of IL-17F rs763780T>C polymorphism with cancer risk except in the CC vs TT genetic model. Although the the risk in the gastric cancer group is higher than that in control group, there were no significant differences on the association of IL-17F rs763780T>C polymorphism with other cancers. Conclusions: Our meta analysis reveal the IL-17A rs763780T>C gene polymorphism is involved in risk of gastric cancer but not other tumor types.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4239-4242
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• 2013

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

• BMB Reports
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• v.42 no.10
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• pp.648-654
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• 2009

Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) genes has been reported to play an important role in protecting host cells from oxidative injury in several model systems. A radish phospholipid hydroperoxide glutathione peroxidase (RsPHGPx) known to have high catalytic activity was applied to mouse 3T3 fibroblasts to determine the protective effects of PHGPx against oxidative injury triggered by hydroperoxides such as hydrogen peroxide ($H_2O_2$), tert-butyl hydroperoxide (t-BHP) and phosphatidylcholine hydroperoxide (PCOOH). We observed that preincubation of cells with RsPHGPx significantly increased cell viability, reduced levels of malondialdehyde (MDA), inhibited generation of reactive oxygen species (ROS), and maintained natural cell shapes after treatment with $H_2O_2$, t-BHP or PCOOH, indicating that the exogenous RsPHGPx can act as an effective hydroperoxide-scavenger and may also protect target cells from oxidative damage. These results suggest the possibility for use of RsPHGPx as a therapeutic protectant.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.235-242
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• 2016

This study tested the association between genotypes of the single nucleotide polymorphism (SNP) marker, rs81437607 and capric acid (FA_C10_0) compositions in longissimus dorsi muscle in pigs. Eighteen fatty acid (FA) compositions were measured in a total of 974 $F_2$ animals among 1,106 $F_2$ progeny produced between Landrace and Jeju Black Pig (JBP). Among FA compositions tested, we identified a cluster of highly significant SNPs for capric acid compositions on 58 Mb position of Sus scrofa chromosome 12 (SSC12) using genome-wide association study (GWAS) with $F_2$ genotypes from SNP panel analysis. GWAS results showed that the rs81437607 was the highest trait-related SNP marker with capric acid levels. Three genotypes (C/C, C/T and T/T) of rs81437607 marker were found in $F_2$ population by further pyrosequencing. Association analysis results showed the significant differences between rs81437607 genotypes and capric acid compositions (P<0.05). The $F_2$ pigs harboring rs81437607 C/C ($0.119{\pm}0.002%$) and C/T ($0.116{\pm}0.002%$) genotypes showed additively higher levels of capric acid content than those of T/T homozygotes ($0.109{\pm}0.002%$) ($P=1.30{\times}10^{-12}$). These results suggested that the genetic variations of rs81437607 may be helpful to find causative variants and assist as molecular genetic markers for improving the capric acid contents in longissimus dorsi muscle in pigs.

• Biomedical Science Letters
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• v.15 no.1
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• pp.101-103
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• 2009

The hepatocyte nuclear factor-$4{\alpha}$ (HNF-$4{\alpha}$), transcription factor involved in the regulation of serum lipid and glucose levels, has recently been reported to be associated with type 2 diabetes. Therefore, we investigated the genotype for the rs1884614 of HNF-$4{\alpha}$ gene in Korean population and compared genotype of patients with control group. 100 patients (Male 63, Female 37), who previously underwent type 2 diabetes (T2DM) and 100 controls (Male 36, Female 64) participated in this study. According to our present study there was no association between rs1884614 polymorphism in HNF-$4{\alpha}$ gene and T2DM in Koreans although other reports showed that HNF-$4{\alpha}$ polymorphisms might be associated with the pathogenesis of T2DM in Pima Indians et al. We assume that this finding should contribute to understanding of type 2 diabetes in Korean population in detail at genetic level.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5871-5876
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• 2013

Background: Single nucleotide polymorphisms (SNPs) occurring in Toll-like receptors (TLRs) may contribute to cancer risk. Many polymorphisms of TLR2 have been studied for associations, but the findings are conflicting. Methodology/Principal Findings: We performed a meta-analysis of 14 studies to confirm the association between TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms and cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of associations. There was no significant association between TLR2+597T>C and cancer risk in the codominant models (CC vs. TT: OR = 1.01, 95%CI = 0.86-1.17, $P_{heterogeneity}=0.148$; CT vs. TT: OR = 0.92, 95%CI = 0.69-1.23, $P_{heterogeneity}$ < 0.001), the recessive model (CC vs. CT+TT: OR = 0.86, 95%CI = 0.67-1.10, $P_{heterogeneity}=0.007$), the dominant model (CC+CT vs. TT: OR = 0.93, 95%CI = 0.76-1.15, $P_{heterogeneity}=0.001$) and the allele model (C vs. T: OR =0.93, 95%CI = 0.81-1.08, $P_{heterogeneity}=0.019$). Similarly, no significant associations between TLR2+1350C>T, Arg753Gln polymorphisms and cancer risk were found. However, in the sub-group analysis of ethnicities, the trend of pooled ORs in Asians was opposite to Caucasians. Conclusions: The present meta-analysis suggests that TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms are not associated with cancer risk.

• Molecules and Cells
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• v.43 no.4
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• pp.350-359
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• 2020

Pathogenic aminoacyl-tRNA synthetases (ARSs) are attractive targets for anti-infective agents because their catalytic active sites are different from those of human ARSs. Mupirocin is a topical antibiotic that specifically inhibits bacterial isoleucyl-tRNA synthetase (IleRS), resulting in a block to protein synthesis. Previous studies on Thermus thermophilus IleRS indicated that mupirocin-resistance of eukaryotic IleRS is primarily due to differences in two amino acids, His581 and Leu583, in the active site. However, without a eukaryotic IleRS structure, the structural basis for mupirocin-resistance of eukaryotic IleRS remains elusive. Herein, we determined the crystal structure of Candida albicans IleRS complexed with Ile-AMP at 2.9 A resolution. The largest difference between eukaryotic and prokaryotic IleRS enzymes is closure of the active site pocket by Phe55 in the HIGH loop; Arg410 in the CP core loop; and the second Lys in the KMSKR loop. The Ile-AMP product is lodged in a closed active site, which may restrict its release and thereby enhance catalytic efficiency. The compact active site also prevents the optimal positioning of the 9-hydroxynonanoic acid of mupirocin and plays a critical role in resistance of eukaryotic IleRS to anti-infective agents.