Tingting Geng

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case–control study from Xi’an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

RTEL1 tagging SNPs and haplotypes were associated with glioma development

AbstractAs glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case–control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF)u2009>u20095% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, Pu2009=u20090.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, Pu2009=u20090.001, OR: 1.33, 95% CI: 1.12-1.58) by χ2 test. It was identified the genotype “GG” of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; Pu2009=u20090.0002), while the genotype “CC” of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; Pu2009=u20090.0003). Furthermore, haplotype “GCT” in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher’s Pu2009=u20090.0005; Pearson’s Pu2009=u20090.0005), and haplotype “ATT” was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher’s Pu2009=u20090.0013; Pearson’s Pu2009=u20090.0013). Two single variants, the genotypes of “GG” of rs6010620 and “CC” of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998

Genetic association between selected cytokine genes and glioblastoma in the Han Chinese population.

BackgroundGlioblastoma (GBM) is the most malignant brain tumor. Many abnormal secretion and expression of cytokines have been found in GBM, initially speculated that the occurrence of GBM may be involved in these abnormal secretion of cytokines. This study aims to detect the association of cytokine genes with GBM.MethodsWe selected seven tag single nucleotide polymorphisms (tSNPs) in six cytokine genes, which previously reported to be associated with brain tumors, and analyzed their association with GBM in a Han Chinese population using χ2 test and genetic model analysis.ResultsWe found two risk tSNPs and one protective tSNP. By χ2 test, the rs1801275 in IL-4R showed an increased risk of GBM. In the genetic model analysis, the genotype “TC” of rs20541 in IL-13 gene showed an increased risk of GBM in over-dominant model (ORu2009=u20092.00; 95% CI, 1.13-3.54, pu2009=u20090.015); the genotype “CT” of rs1800871 in the IL-10 gene showed a decrease risk in the over-dominant model (ORu2009=u20090.57; 95% CI, 0.33 – 0.97; pu2009=u20090.037). The genotype “AG” of rs1801275 in the IL-4R gene showed an increase risk in over-dominant model (ORu2009=u20092.29; 95% CI, 1.20 - 4.35; pu2009=u20090.0081) We further analyzed whether the six cytokine genes have a different effect on the disease in gender specific population, and found that the allele “G” of rs2243248 in the IL-4 gene showed a decrease risk of GBM in female (ORu2009=u20090.35, 95% CI, 0.13 - 0.94, pu2009=u20090.0032), but the allele “T” showed a decrease risk in male (ORu2009=u20090.30, 95% CI, 0.17 - 0.53, pu2009=u20090.0032).ConclusionsOur findings, combined with previously reported results, suggest that cytokine genes have potential role in GBM development, which may be useful to early prognostics for GBM in the Han Chinese population.

Genetic variation in the TP63 gene is associated with lung cancer risk in the Han population

Lung cancer is one of the most common malignant tumors that seriously threaten human health. Current evidence suggests that heredity contributes to the progression of lung cancer. To investigate and validate potential genetic associations with the risk of lung cancer, we conducted a case–control study including 309 cases and 310 controls from Xi’an City, which is located in northwest China, and genotyped six SNPs in five genes, which are related to metabolic process. Overall, our results show that the SNP rs10937405 was associated with a decreased occurrence of lung cancer (ORu2009=u20090.72; 95xa0% CIu2009=u20090.56–0.92; pu2009=u20090.009). In the genetic models analysis, we found that genotype “CT” of rs10937405 in TP63 was associated with a decreased lung cancer risk (ORu2009=u20090.71; 95xa0% CI, 0.51–0.99; pu2009=u20090.031); the genotype “TT” of rs10937405 showed a decreased lung cancer risk in the co-dominant model (ORu2009=u20090.53; 95xa0% CI, 0.30–0.95; pu2009=u20090.031). The genotype “CT-TT” of rs10937405 also showed a decreased lung cancer risk in the dominant model (ORu2009=u20090.67; 95xa0% CI, 0.49–0.92; pu2009=u20090.014) and the log-additive model (ORu2009=u20090.72; 95xa0% CI, 0.56–0.92; pu2009=u20090.0085). The genotype “CC-CT” of rs10937405 confers a higher risk of lung cancer for males than females. Our results, combined with those from previous studies, suggest that genetic variation in TP63 may influence lung cancer susceptibility in the Han population.

Correlation of CLPTM1L polymorphisms with lung cancer susceptibility and response to cisplatin-based chemotherapy in a Chinese Han population.

The implication of genetic factors in predisposition to cancer is a recognized fact. The Cleft lip and palate transmembrane 1-like (CLPTM1L) gene resides in a locus in the chromosome 5p15.33 region that is associated with lung cancer susceptibility and has a role in carcinogenesis. We conducted a case-control study in a Chinese population of 309 pathologically confirmed lung cancer patients and 310 controls to investigate the effect of variant genotypes within the CLPTM1L locus on susceptibility to lung cancer and sensitivity to cisplatin-based chemotherapy. We genotyped nine single nucleotide polymorphisms (SNPs) within the CLPTM1L locus and examined their correlation with lung cancer risk and treatment response using χ2 and unconditional logistic regression analysis. We identified rs451360 as a novel SNP associated with lung cancer risk in the Chinese Han population. The “T” allele of rs451360 was associated with decreased risk of lung cancer (pu2009=u20090.007, odd ratio (OR)u2009=u20090.59, 95xa0% confidence interval (CI): 0.40–0.87). Significant multiplicative interactions were observed between gender and polymorphisms of rs402710, the “T/T” genotype of which was associated with decreased lung cancer risk in male patients (pu2009=u20090.016, ORu2009=u20090.35, 95xa0% CI: 0.17–0.73). CLPTM1L polymorphisms did not affect the tumor sensitivity to cisplatin combination chemotherapy in our study patients. The results of the present study suggest a potential association between CLPTM1L variants and lung cancer risk in the Chinese Han populations.

Genetic association of PLCE1, C11orf92-C11orf93, and NOC3L with colorectal cancer risk in the Han population

Colorectal cancer (CRC) is a common malignant tumor that is influenced by an interaction between genetic and environmental factors. Currently, the inherited factors of CRC are unclear. Our study selected 19 tag single nucleotide polymorphisms (tSNPs) to investigate whether they were associated with CRC in the Han population. In this Han Chinese case–control study, we genotyped 203 CRC cases and 296 controls using Sequenom MassARRAY technology and analyzed their associations with CRC using χ2 tests, SNPStats software, and SHEsis software. Based on χ2 tests, PLCE1-rs2077218, rs11187877 (pu2009=u20090.049) and C11orf92-C11orf93-rs3802842 (pu2009=u20090.023) correlate with CRC risk. In the genetic model analyses, we found the genotype “CC” of rs3802842 in C11orf92-C11orf93 may significantly increase CRC risk in the recessive model (pu2009=u20090.0071), whereas “GT” of rs17109928 in NOC3L may decrease the risk in the over-dominant model (pu2009=u20090.0091). Using SHEsis software, we found PLCE1 and NOC3L are strongly linked, and the “GCCATTCTGTC” haplotype may increase the risk of CRC (pu2009=u20090.049). We found three genes (PLCE1, C11orf92-C11orf93, and NOC3L) are associated with CRC susceptibility. In combination with previous reports, our results suggest that these genes may be associated with CRC in the Han population.

Polymorphisms in ESR1 and FLJ43663 are associated with breast cancer risk in the Han population

Breast cancer is a heterogeneous disease which is influenced by genetic, environmental, and lifestyle factors. Genetic susceptibility is likely to be due to variants conferring more moderate risks. To identify susceptibility alleles, we conducted a case–control association study in 185 breast cancer cases and 199 controls in the Han population. We genotyped 14 tagging single nucleotide polymorphisms previously implicated in breast cancer using Sequenom MassARRAY SNP genotyping method and identified rs3734805 in the ESR1 gene and rs2048672 in the FLJ43663 gene were associated with breast cancer risk. Allele “C” of rs3734805 was associated with increased breast cancer progression by χ2 test and additive model analysis (ORu2009=u20091.36; 95xa0% CI, 1.01–1.82; pu2009=u20090.042). Using recessive model analysis, we found that genotype “GG” of rs2048672 was the protective genotype during breast cancer progression (ORu2009=u20090.55; 95xa0% CI, 0.32–0.95; pu2009=u20090.029). Our results provide additional insights into the opposing roles of the ESR1 and FLJ43663 genes in breast cancer onset and progression.

CCDC26 Gene Polymorphism and Glioblastoma Risk in the Han Chinese Population

BACKGROUNDnGlioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12- 15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM.nnnMATERIALS AND METHODSnWe genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci.nnnRESULTSnWe found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, CG and CGGAG were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model.nnnCONCLUSIONSnOur results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese.

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

AIMSnAlterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer.nnnMETHODSnUsing multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves.nnnRESULTSnThe mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage.nnnCONCLUSIONSnThe mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.

Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China

BackgroundIndividual response to medications varies significantly among different populations, and great progress in understanding the molecular basis of drug action has been made in the past 50 years. The field of pharmacogenomics seeks to elucidate inherited differences in drug disposition and effects. While we know that different populations and ethnic groups are genetically heterogeneous, we have not found any pharmacogenomics information regarding minority groups, such as the Tajik ethnic group in northwest China.ResultsWe genotyped 85 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 100 unrelated, healthy Tajiks from the Xinjiang Uygur Autonomous Region and compared our data with HapMap data from four major populations around the world: Han Chinese (CHB), Japanese in Tokyo (JPT), Utah Residents with Northern and Western European Ancestry (CEU), and Yorubia in Ibadan, Nigeria (YRI). We found that Tajiks differed from CHB, JPT and YRI in 30, 32, and 32 of the selected VIP genotypes respectively (p < 0.005), while differences between Tajiks and CEU were found in only 6 of the genotypes (p < 0.005). Haplotype analysis also demonstrated differences between the Tajiks and the other four populations.ConclusionOur results contribute to the pharmacogenomics database of the Tajik ethnic group and provide a theoretical basis for safer drug administration that may be useful for diagnosing and treating disease in this population.