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Meta-analysis of Associations Between four Polymorphisms in the Matrix Metalloproteinases Gene and Gastric Cancer Risk

  • Yang, Teng-Fei;Guo, Lin;Wang, Qiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1263-1267
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    • 2014
  • Background: Matrix metalloproteinases (MMPs) play important roles in pathogenesis and development of cancer. Recently, many studies have show associations between polymorphisms in the promoter regions of MMPs and risk of gastric cancer. The present meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and gastric cancer risk. Methods: A computerized literature search was conducted in databases of Med-line, Embase, Science Citation Index and PubMed till June 2013 for any MMP genetic association study of gastric cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated for each gene under dominant and recessive models, and heterogeneity between studies was assessed using the Q test and $I^2$ value. Overall and subgroup analyses according to ethnicity were carried out with Stata 12.0. Results: 14 reports covering 8,146 patients (2,980 in the case group and 5,166 in the control group) were included in the present meta-analysis. We found that the MMP-7 (-181A>G) polymorphism increased the gastric cancer risk in therecessive model (GG vs. AA/AG, OR=1.768, 95% CI =1.153-2.712). For MMP2 -1306 C>T, MMP1-1607 1G/2G, and MMP9-1 562 C>T, there were no associations between these polymorphisms and the risk of gastric cancer under dominant or recessive models. Conclusion: This meta-analysis suggested that the MMP7-181 A>G polymorphism may contribute to gastric cancer susceptibility. More studies are needed, especially in Europeans, in the future.

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

  • Cao, Xue-Yuan;Jia, Zhi-Fang;Cao, Dong-Hui;Kong, Fei;Jin, Mei-Shan;Suo, Jian;Jiang, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5713-5718
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    • 2013
  • Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Platinum-based Chemotherapy Response of Advanced Non-small Cell Lung Cancers in a Chinese Population

  • Xu, Jia-Li;Wang, Zhen-Wu;Hu, Ling-Min;Yin, Zhi-Qiang;Huang, Ming-De;Hu, Zhi-Bin;Shen, Hong-Bing;Shu, Yong-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2157-2162
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    • 2012
  • Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients

  • Sa-Nguanraksa, Doonyapat;Suntiparpluacha, Monthira;Kulprom, Anchalee;Kummalue, Tanawan;Chuangsuwanich, Tuenjai;Avirutnan, Panissadee;O-Charoenrat, Pornchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2935-2940
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    • 2016
  • Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

Alteration and Mineralization in the Xiaoxinancha Porphyry Copper Deposit, Yianbin, China: Fluid Inclusion and Sulfur Isotope Study (중국 연변 쇼시난차 반암동 광상의 광화작용 및 변질작용: 유체포유물 및 황동위원소 연구)

  • Seong-Taek Yun;Chil-Sup So;Bai-Lu Jin;Chul-Ho Heo;Seung-Jun Youm
    • Economic and Environmental Geology
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    • v.35 no.3
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    • pp.211-220
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    • 2002
  • The Xiaoxinancha Cu-Au deposit in the Jilin province, located in NNE 800 km of Beijing, is hosted by diorite. The ore mineralization of Xiaoxinancha Cu-Au deposit show a stockwork occurrence that is concentrated on the potassic and phyllic alteration zones. The Xiaoxinancha Cu-Au deposit in the south is being mined with its reserves grading 0.8% Cu, 3.64 g/t Au and 16.8 g/t Ag and in the north, grading 0.63% Cu, 3.80 g/t Au and 6.8 glt Ag. The alteration assemblage occurs as a supergene blanket over deposit. Hydrothermal alteration at the Xiaoxinancha Cu-Au deposit is centered about the stock and was extensively related to the emplacement of the stock. Early hydrothermal alteration was dominantly potassic and followed by propylitic alteration. Chalcocite, often associated with hematite, account for the ore-grade copper, while chalcopyrite, bornite, quartz, epidote, chlorite and calcite constitute the typical gangue assemblage. Other minor opaque phases include pyrite, marcasite, native gold, electrum, hessite, hedleyite, volynskite, galenobismutite, covellite and goethite. Fluid inclusion data indicate that the formation of this porphyry copper deposit is thought to be a result of cooling followed by mixing with dilute and cooler meteoric water with time. In stage II vein, early boiling occurred at 497$^{\circ}$C was succeeded by the occurrence of halite-bearing type III fluid inclusion with homogenization temperature as much as 100$^{\circ}$C lower. The salinities of type 1II fluid inclusion in stage II vein are 54.3 to 66.9 wt.% NaCI + KCI equiv. at 383$^{\circ}$ to 495$^{\circ}$C, indicating the formation depth less than 1 km. Type I cupriferous fluids in stage III vein have the homogenization temperatures and salinity of 168$^{\circ}$ to 365$^{\circ}$C and 1.1 to 9.0 wt.% NaCI equiv. These fluid inclusions in stage III veins were trapped in quartz veins containing highly fractured breccia, indicating the predominance of boiling evidence. This corresponds to hydrostatic pressure of 50 to 80 bars. The $\delta$$^{34}S$ value of sulfide minerals increase slightly with paragenetic time and yield calculated $\delta$$^{34}S_{H2S}$ values of 0.8 to 3.7$\textperthousand$. There is no mineralogical evidence that fugacity of oxygen decreased, and it is thought that the oxygen fugacity of the mineralizing fluids have been buffered through reaction with magnetite. We interpreted the range of the calculated $\delta$$^{34}S_{H2S}$ values for sulfides to represent the incorporation of sulfur from two sources into the Xiaoxinancha Cu-Au hydrothermal fluids: (1) an isotopically light source with a $\delta$$^{34}S$ value of I to 2$\textperthousand$, probably a Mesozoic granitoid related to the ore mineralization. We can infer from the fact that diorite as the host rock in the Xiaoxinancha Cu-Au deposit area intruded plagiogranite; (2) an isotopically heavier source with a $\delta$$^{34}S$ value of > 4.0$\textperthousand$, probably the local porphyry.

Melanocyte-stimulating Hormone Receptor (MC1R) Genotype and Its Effects on Coat Color in Korean Jindo Dogs

  • Hong, Kyung-Won;Kim, Sang-Wook;Jang, Hong-Chul;Yang, Seung-Min;Shin, Young-Bin;Hong, Yoon-Hye;Kim, Jong-Seok;Oh, Seok-Il;Choi, Yoon-Ju;Chung, Dong-Hee;Yang, Boh-Suk;Lee, Ji-Woong;Choi, Bong-Hwan
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.8
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    • pp.1078-1084
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    • 2009
  • The Jindo dog is a Korean natural monument and is recognized by the Fédération Cynologique Internationale. A prominent feature is the diverse coat color within the breed. To analyze the genetic basis of variation in the Jindo coat color, we sequenced the protein-coding regions of the melanocortin 1 receptor gene (MC1R). The MC1R coding sequence was determined from 154 dogs in five breeds (Jindo, Labrador Retriever, English Springer Spaniel, Belgian Malinois, and German Shepherd). To confirm the genetic structure of sampled populations, we tested for Hardy-Weinberg equilibrium (HWE) and computed $F_{st}$ The sample populations did not significantly deviate from HWE. $F_{st}$ was 0.02 between white and fawn Jindo dogs; this was lower than $F_{st}$ between breeds. Six single nucleotide polymorphisms (SNPs) were detected in the MC1R coding region. Among the six SNPs, five were non-synonymous (S90G, T105A, Q159P, M264V, and R306ter) and one was synonymous SNP (Y298Y). From the SNPs, we predicted four haplotypes (H1, H2, H3, and H4) for Jindo MC1R. Jindo dogs had different haplotypes corresponding to different coat colors. H1 was frequently observed in white Jindo dogs with an odds ratio of 5.03 (95% CI: 2.27-11.18, p<0.0001), whereas H2 and H4 were observed only in fawn Jindo dogs. Our findings indicate that SNP haplotype can influence coat color. Knowledge of MC1R haplotypes can help discriminate white and fawn coats in Jindo dogs. We hope this report will trigger more research into the genetics of this traditional Korean dog and will be a reference for dogs of Asian origin. Also, our results will provide a useful genetic marker for Jindo dog breeders who have selected for specific colors.

Is there an Association between Variants in Candidate Insulin Pathway Genes IGF-I, IGFBP-3, INSR, and IRS2 and Risk of Colorectal Cancer in the Iranian Population?

  • Karimi, Khatoon;Mahmoudi, Touraj;Karimi, Negar;Dolatmoradi, Hesamodin;Arkani, Maral;Farahani, Hamid;Vahedi, Mohsen;Parsimehr, Elham;Dabiri, Reza;Nobakht, Hossein;Asadi, Asadollah;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5011-5016
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    • 2013
  • Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. Materials and Methods: The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Results: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). Conclusions: These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.

Mesothermal Gold Mineralization in the Boseong-Jangheung area, Chollanamdo-province (전라남도 보성-장흥지역의 중열수 금광화작용)

  • 허철호;윤성택;소칠섭
    • Economic and Environmental Geology
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    • v.35 no.5
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    • pp.379-393
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    • 2002
  • Within the Boseong-Jangheung area of Korea, five hydrothermal gold (-silver) quartz vein deposits occur. They have the characteristic features as follows: the relatively gold-rich nature of e1ectrurns; the absence of Ag-Sb( -As) sulfosalt mineral; the massive and simple mineralogy of veins. They suggest that gold mineralization in this area is correlated with late Jurassic to Early Cretaceous, mesothermal-type gold deposits in Korea. Fluid inclusion data show that fluid inclusions in stage I quartz of the mine area homogenize over a wide temperature range of 200$^{\circ}$ to 460$^{\circ}$C with salinities of 0.0 to 13.8 equiv. wt. % NaCI. The homogenization temperature of fluid inclusions in stage II calcite of the mine area ranges from 150$^{\circ}$ to 254$^{\circ}$C with salinities of 1.2 to 7.9 equiv. wt. % NaCI. This indicates a cooling of the hydrothermal fluid with time towards the waning of hydrothermal activity. Evidence of fluid boiling including CO2 effervescence indicates that pressures during entrapment of auriferous fluids in this area range up to 770 bars. Calculated sulfur isotope composition of auriferous fluids in this mine area (${\delta}^34S$_{{\Sigma}S}$$\textperthousand$) indicates an igneous source of sulfur in auriferous hydrothermal fluids. Within the Sobaegsan Massif, two representative mesothermal-type gold mine areas (Youngdong and Boseong-Jangheung areas) occur. The ${\delta}^34S values of sulfide minerals from Youngdong area range from -6.6 to 2.3$\textperthousand$ (average=-1.4$\textperthousand$, N=66), and those from BoseongJangheung area range from -0.7 to 3.6$\textperthousand$ (average=1.6$\textperthousand$, N=39). These i)34S values of both areas are comparatively lower than those of most Korean metallic ore deposits (3 to 7TEX>$\textperthousand$). And, within the Sobaegsan Massif, the ${\delta}^34S values of Youngdong area are lower than those of Boseong-Jangheung area. It is inferred that the difference of ${\delta}^34S values within the Sobaegsan Massif can be caused by either of the following mechanisms: (1) the presence of at least two distinct reservoirs (both igneous, with ${\delta}^34S values of < -6 $\textperthousand$ and 2$\pm$2 %0) for Jurassic mesothermal-type gold deposits in both areas; (2) different degrees of the mixing (assimilation) of 32S-enriched sulfur (possibly sulfur in Precambrian pelitic basement rocks) during the generation and/or subsequent ascent of magma; and/or (3) different degrees of the oxidation of an H2S-rich, magmatically derived sulfur source ${\delta}^34S = 2$\pm$2$\textperthousand$) during the ascent to mineralization sites. According to the observed differences in ore mineralogy (especially, iron-bearing ore minerals) and fluid inclusions of quartz from the mesothermal-type deposits in both areas, we conclude that pyrrhotite-rich, mesothermal-type deposits in the Youngdong area formed from higher temperatures and more reducing fluids than did pyrite(-arsenopyrite)-rich mesothermal-type deposits in the Boseong-Jangheung area. Therefore, we prefer the third mechanism than others because the ${\delta}^34S values of the Precambrian gneisses and Paleozoic sedimentary rocks occurring in both areas were not known to the present. In future, in order to elucidate the provenance of ore sulfur more systematically, we need to determine ${\delta}^34S values of the Precambrian metamorphic rocks and Paleozoic sedimentary rocks consisting the basement of the Korean Peninsula including the Sobaegsan Massif.