Yanhong Liu - Academia.edu (original) (raw)

Papers by Yanhong Liu

Research paper thumbnail of associated with risk of lung cancer in a Chinese population

Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor... more Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) dampens the inflammation cascade and inhibits tumor growth of the lung, suggesting that it has tumor suppressor functions. We performed a case-control study of 500 incident lung cancer cases and 517 age and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of 11 selected single nucleotide polymorphisms (SNPs) of PPAR-γ in the etiology of lung cancer. We found that decreased lung cancer risk was statistically significantly associated with seven SNPs (P = 0.0004 for rs13073869 and 0.0130 for rs1899951 in a dominant model; P = 0.0310 for rs4135247 in a log-additive model; and P = 0.0468 for rs2972162, 0.0175 for rs709151, 0.0172 for rs11715541 and 0.0386 for rs1175543 in an overdominant model). Consistent with these results of single-locus analysis, both the haplotype and diplotype analyses revealed a protective effect of the haplotype 'AGA' and 'AAA' of rs13073869, rs1899951 and rs4135247. Furthermore, we observed a statistically significant interaction between the rs1899951 and cigarette smoking. Our results indicate that PPAR-γ polymorphisms and their interaction with smoking may contribute to the etiology of lung cancer. These findings need to be validated in larger, preferably population-based, studies including different ethnic groups. by guest on July 12, 2015 http://carcin.oxfordjournals.org/ Downloaded from

Research paper thumbnail of Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

Human Genetics

The risk of glioma has consistently been shown to be increased twofold in relatives of patients w... more The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication ...

Research paper thumbnail of Genetic Modulation of Neurocognitive Function in Glioma Patients

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 22, 2015

Accumulating evidence supports the contention that genetic variation is associated with neurocogn... more Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients. To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test-Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined. Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive f...

Research paper thumbnail of Molecular consequences of Ds insertion into and excision from the helix-loop-helix domain of the maize R gene

Genetics, 1998

The R and B proteins of maize are required to activate the transcription of several genes in the ... more The R and B proteins of maize are required to activate the transcription of several genes in the anthocyanin biosynthetic pathway. To determine the structural requirements for R function in vivo, we are exploiting its sensitive mutant phenotype to identify transposon (Ds) insertions that disrupt critical domains. Here we report that the ability of the r-m1 allele to activate transcription of at least three structural genes is reduced to only 2% of wild-type activity because of a 396-bp Ds element in helix 2 of the basic helix-loop-helix (bHLH) motif. Residual activity likely results from the synthesis of a mutant protein that contains seven additional amino acids in helix 2. This protein is encoded by a transcript where most of the Ds sequence has been spliced from pre-mRNA. Two phenotypic classes of stable derivative alleles, very pale and extremely pale, condition <1% of wild-type activity as a result of the presence of two- and three-amino-acid insertions, respectively, at the...

Research paper thumbnail of The cascade mechanisms of nitric oxide as a second messenger of ultraviolet B in inhibiting mesocotyl elongations

Photochemistry and photobiology, 2003

In this report, a number of physiological aspects was examined during developmental growth of mai... more In this report, a number of physiological aspects was examined during developmental growth of maize seedling's mesocotyl. It was found that ultraviolet B (UVB) radiation was able to significantly induce nitric oxide synthase (NOS) activities and speedup the release of apparent nitric oxide (NO) of mesocotyl and that exogenous NO donor's rhizospheric treatments may mimic the responses of the mesocotyl to UVB radiation, such as the inhibition of mesocotyl elongation, the decrease in exo- and endoglucanase activities and the increase in protein content of cell wall of mesocotyl. When the seedlings were treated with N-nitro-L-arginine, an inhibitor of NOS, the mesocotyl elongation was promoted, the exo- and endoglucanase activities were raised and the protein content was reduced. However, under UVB radiation, the effects of exogenous NO on several physiological aspects of mesocotyl were similar to those of exogenous reactive oxygen species (ROS) eliminator, N-acetyl-cysteine. Al...

Research paper thumbnail of Germline mutations in shelterin complex genes are associated with familial glioma

Journal of the National Cancer Institute, 2015

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy... more Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

Research paper thumbnail of IDENTIFICATION OF GENOMIC SIGNATURES FOR THE DESIGN OF ASSAYS FOR THE DETECTION AND MONITORING OF ANTHRAX THREATS

Biocomputing 2005 - Proceedings of the Pacific Symposium, 2005

Sequences that are present in a given species or strain while absent from or different in any oth... more Sequences that are present in a given species or strain while absent from or different in any other organisms can be used to distinguish the target organism from other related or un-related species. Such DNA signatures are particularly important for the identification of genetic source of drug resistance of a strain or for the detection of organisms that can be used as biological agents in warfare or terrorism. Most approaches used to find DNA signatures are laboratory based, require a great deal of effort and can only distinguish between two organisms at a time. We propose a more efficient and cost-effective bioinformatics approach that allows identification of genomic fingerprints for a target organism. We validated our approach using a custom microarray, using sequences identified as DNA fingerprints of Bacillus anthracis. Hybridization results showed that the sequences found using our algorithm were truly unique to B. anthracis and were able to distinguish B. anthracis from its close relatives B. cereus and B. thuringiensis.

Research paper thumbnail of Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Scientific Reports, 2015

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary br... more Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

Research paper thumbnail of The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers

Science of the Total Environment, 2007

Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure,... more Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such knowledge could benefit us in understanding the inter-individual difference in the mechanism of PAHs-induced carcinogenesis. We investigated the influence of gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from two coking plants in south China. After adjustment for age, plant, level of occupational exposure, body mass index, level of education, alcohol consumption, cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 −3263TNG (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of urinary 1-OHP (Geometric mean, μmol/mol creatinine) in the homozygous major variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 −3263TNG and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92, 4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA carriers (5.17 vs. 3.64 μmol/mol creatinine, p = 0.038), as well as in the case with UGT1A1 −3263TNG TG/GG carriers (5.67 vs. 3.38 μmol/mol creatinine, p = 0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms were associated with urinary 1-OHP concentrations in Chinese coke oven workers. No influence was found in the association between urinary 1-OHP and other genetic polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this population.

Research paper thumbnail of Genome-wide association study identifies six susceptibility loci for glioma

Research paper thumbnail of Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population

Pharmacogenetics and Genomics, 2009

Research paper thumbnail of Genetic variations in EGF and EGFR and glioblastoma outcome

Neuro-Oncology, 2010

Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete ta... more Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94 -1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99 -1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

Research paper thumbnail of Molecular Cloning and Characterization of a Tobacco MAP Kinase Kinase That Interacts with SIPK

Molecular Plant-Microbe Interactions, 2000

A tobacco MAP kinase termed SIPK (salicylic acidinduced protein kinase) is activated in response ... more A tobacco MAP kinase termed SIPK (salicylic acidinduced protein kinase) is activated in response to a variety of stress signals, including pathogen attack and wounding (S. Zhang and D. F. Klessig, Proc. Natl. Acad. Sci. USA 95:7225-7230, 1998; S. Zhang and D. F. Klessig, Proc. Natl. Acad. Sci. USA 95:7433-7438, 1998). Using the yeast two-hybrid system, we have identified a gene encoding a

Research paper thumbnail of Effects of nitric oxide on growth of maize seedling leaves in the presence or absence of ultraviolet-B radiation

Journal of Plant Physiology, 2005

The leaves of maize seedlings were used to measure leaf biomass including leaf length, width and ... more The leaves of maize seedlings were used to measure leaf biomass including leaf length, width and weight, and to examine the relationship between nitric oxide (NO) synthase activity in microsomes and cytosol to the exo- and endo-beta-glucanase activity during growth. It was found that ultraviolet-B radiation (UV-B radiation) strongly induced nitric oxide synthase (NOS) activity but caused both a decrease of leaf biomass and exo- or endo-beta-glucanase activity. In contrast, the NOS inhibitor and NO donor largely decreased the activity of NOS in non-irradiated seedlings. The inhibitor also reduced exo- and endo-beta-glucanase activity and leaf biomass while the donor increased the enzyme activity and leaf biomass under normal conditions. Alternatively, under ultraviolet-B, the additional inhibitor of NOS and NO donor appeared to compromise the effects of ultraviolet-B on glucanase activity and leaf biomass, making the relationship between NOS activity and glucanase activity negatively correlated. This suggests that the changes of NOS activity showed a positive correlation to glucanase activity and leaf biomass in the absence of ultraviolet-B, but a negative correlation to ultraviolet-B irradiation and NO donor treatment alone. It is assumed that exo- and endogenous NO is responsible for the up-regulation of regular growth and development without ultraviolet-B. Under UV-B radiation, however, it might function as a signaling molecule of ultraviolet-B inhibiting leaf growth of maize seedlings to carry out stress-signaling transduction.

Research paper thumbnail of Allele Frequency Distribution at Seven Y-Chromosomal STR Loci Among Five Ethnic Groups from Northwest China

Journal of Forensic Sciences, 2005

Research paper thumbnail of Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 Genes Involved in the Double-Strand Break Repair Pathway Predict Glioblastoma Survival

Journal of Clinical Oncology, 2010

Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival.... more Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment.

Research paper thumbnail of Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics

Journal of Applied Genetics, 2011

Double minute chromosomes (DMs) are the cytogenetic hallmark of extra-chromosomal genomic amplifi... more Double minute chromosomes (DMs) are the cytogenetic hallmark of extra-chromosomal genomic amplification. The frequency of DMs in primary cancer and the cytogenetic features of DMs-positive primary cancer cases are largely unknown. To unravel these issues, we retrieved the Mitelman database and analyzed all DMs-positive primary cancerous karyotypes (787 karyotypes). The overall frequency of DMs is 1.4% (787 DMs-positive cases; total 54,398 cases). We found that DMs have the highest frequency in adrenal carcinoma (28.6%, topography) and neuroblastoma (31.7%, morphology). The frequencies of DMs in each tumor were much lower than in previous reports. The frequency of DMs in malignant cancers is significantly higher than in benign cancers, which confirms that DMs are malignant cytogenetic markers. DMs combined cytogenetic abnormalities are identified and sorted into two groups by principal component analysis (PCA), with one group containing -4, -5, -8, -9, -10, -13, -14, -15, -16, -17, -18, -20, -21, and -22, and the other containing -1p, -5q, +7, and +20. The prominent imbalance in DMs-positive cancer cases is chromosome loss. However, DMs-positive cancer cases, deriving from different morphologic cancers, cannot be clearly divided into subgroups. Our large database analysis provides novel knowledge of DMs and their combined cytogenetic abnormalities in primary cancer.

Research paper thumbnail of Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population

International Journal of Cancer, 2011

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic... more Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G1405C, G-634C) [odds ratio (OR) 5 1.29; 95% confidence interval (CI) 5 1.04-1.58; GC/CC vs. GG] and rs3025030 (OR 5 2.21; 95% CI 5 1.18-4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR 5 0.66; 95% CI 5 0.47-0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20-40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p 5 0.002, p corrected 5 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (p trend 5 8.4 3 10 25 ). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

Research paper thumbnail of Allergy and glioma risk: Test of association by genotype

International Journal of Cancer, 2011

between atopy and glioma risk these observations have been based on self-reporting of allergic co... more between atopy and glioma risk these observations have been based on self-reporting of allergic conditions raising the possibility that associations may be non-causal and arise as a consequence of bias, reverse causation or other artefacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analysed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13, and 17q21 that are associated with asthma or eczema risk at P < 5.0 x 10 -7 . The SNP rs7216389, which tags the 3' flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01-1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses.

Research paper thumbnail of XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital-based case-control study

International Journal of Cancer, 2009

In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in th... more In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype-based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancerfree controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR 5 1.44, 95% CI 5 1.15-1.80, p 5 0.001 and CT/TT versus CC: adjusted OR 5 1.66, 95% CI 5 1.12-2.46, p 5 0.013, respectively). Consistent with these results, XRCC3 haplotype ''GGCC'' containing rs861530 G allele and haplotype ''AGTC'' containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype ''AGCC'' (adjusted OR 5 1.35, 95% CI 5 1.14-1.58, p 5 0.000 and adjusted OR 5 1.67, 95% CI 5 1.11-2.52, p 5 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk. ' 2009 UICC

Research paper thumbnail of associated with risk of lung cancer in a Chinese population

Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor... more Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) dampens the inflammation cascade and inhibits tumor growth of the lung, suggesting that it has tumor suppressor functions. We performed a case-control study of 500 incident lung cancer cases and 517 age and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of 11 selected single nucleotide polymorphisms (SNPs) of PPAR-γ in the etiology of lung cancer. We found that decreased lung cancer risk was statistically significantly associated with seven SNPs (P = 0.0004 for rs13073869 and 0.0130 for rs1899951 in a dominant model; P = 0.0310 for rs4135247 in a log-additive model; and P = 0.0468 for rs2972162, 0.0175 for rs709151, 0.0172 for rs11715541 and 0.0386 for rs1175543 in an overdominant model). Consistent with these results of single-locus analysis, both the haplotype and diplotype analyses revealed a protective effect of the haplotype 'AGA' and 'AAA' of rs13073869, rs1899951 and rs4135247. Furthermore, we observed a statistically significant interaction between the rs1899951 and cigarette smoking. Our results indicate that PPAR-γ polymorphisms and their interaction with smoking may contribute to the etiology of lung cancer. These findings need to be validated in larger, preferably population-based, studies including different ethnic groups. by guest on July 12, 2015 http://carcin.oxfordjournals.org/ Downloaded from

Research paper thumbnail of Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

Human Genetics

The risk of glioma has consistently been shown to be increased twofold in relatives of patients w... more The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication ...

Research paper thumbnail of Genetic Modulation of Neurocognitive Function in Glioma Patients

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 22, 2015

Accumulating evidence supports the contention that genetic variation is associated with neurocogn... more Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients. To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test-Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined. Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive f...

Research paper thumbnail of Molecular consequences of Ds insertion into and excision from the helix-loop-helix domain of the maize R gene

Genetics, 1998

The R and B proteins of maize are required to activate the transcription of several genes in the ... more The R and B proteins of maize are required to activate the transcription of several genes in the anthocyanin biosynthetic pathway. To determine the structural requirements for R function in vivo, we are exploiting its sensitive mutant phenotype to identify transposon (Ds) insertions that disrupt critical domains. Here we report that the ability of the r-m1 allele to activate transcription of at least three structural genes is reduced to only 2% of wild-type activity because of a 396-bp Ds element in helix 2 of the basic helix-loop-helix (bHLH) motif. Residual activity likely results from the synthesis of a mutant protein that contains seven additional amino acids in helix 2. This protein is encoded by a transcript where most of the Ds sequence has been spliced from pre-mRNA. Two phenotypic classes of stable derivative alleles, very pale and extremely pale, condition <1% of wild-type activity as a result of the presence of two- and three-amino-acid insertions, respectively, at the...

Research paper thumbnail of The cascade mechanisms of nitric oxide as a second messenger of ultraviolet B in inhibiting mesocotyl elongations

Photochemistry and photobiology, 2003

In this report, a number of physiological aspects was examined during developmental growth of mai... more In this report, a number of physiological aspects was examined during developmental growth of maize seedling's mesocotyl. It was found that ultraviolet B (UVB) radiation was able to significantly induce nitric oxide synthase (NOS) activities and speedup the release of apparent nitric oxide (NO) of mesocotyl and that exogenous NO donor's rhizospheric treatments may mimic the responses of the mesocotyl to UVB radiation, such as the inhibition of mesocotyl elongation, the decrease in exo- and endoglucanase activities and the increase in protein content of cell wall of mesocotyl. When the seedlings were treated with N-nitro-L-arginine, an inhibitor of NOS, the mesocotyl elongation was promoted, the exo- and endoglucanase activities were raised and the protein content was reduced. However, under UVB radiation, the effects of exogenous NO on several physiological aspects of mesocotyl were similar to those of exogenous reactive oxygen species (ROS) eliminator, N-acetyl-cysteine. Al...

Research paper thumbnail of Germline mutations in shelterin complex genes are associated with familial glioma

Journal of the National Cancer Institute, 2015

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy... more Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

Research paper thumbnail of IDENTIFICATION OF GENOMIC SIGNATURES FOR THE DESIGN OF ASSAYS FOR THE DETECTION AND MONITORING OF ANTHRAX THREATS

Biocomputing 2005 - Proceedings of the Pacific Symposium, 2005

Sequences that are present in a given species or strain while absent from or different in any oth... more Sequences that are present in a given species or strain while absent from or different in any other organisms can be used to distinguish the target organism from other related or un-related species. Such DNA signatures are particularly important for the identification of genetic source of drug resistance of a strain or for the detection of organisms that can be used as biological agents in warfare or terrorism. Most approaches used to find DNA signatures are laboratory based, require a great deal of effort and can only distinguish between two organisms at a time. We propose a more efficient and cost-effective bioinformatics approach that allows identification of genomic fingerprints for a target organism. We validated our approach using a custom microarray, using sequences identified as DNA fingerprints of Bacillus anthracis. Hybridization results showed that the sequences found using our algorithm were truly unique to B. anthracis and were able to distinguish B. anthracis from its close relatives B. cereus and B. thuringiensis.

Research paper thumbnail of Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Scientific Reports, 2015

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary br... more Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

Research paper thumbnail of The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers

Science of the Total Environment, 2007

Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure,... more Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such knowledge could benefit us in understanding the inter-individual difference in the mechanism of PAHs-induced carcinogenesis. We investigated the influence of gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from two coking plants in south China. After adjustment for age, plant, level of occupational exposure, body mass index, level of education, alcohol consumption, cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 −3263TNG (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of urinary 1-OHP (Geometric mean, μmol/mol creatinine) in the homozygous major variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 −3263TNG and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92, 4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA carriers (5.17 vs. 3.64 μmol/mol creatinine, p = 0.038), as well as in the case with UGT1A1 −3263TNG TG/GG carriers (5.67 vs. 3.38 μmol/mol creatinine, p = 0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms were associated with urinary 1-OHP concentrations in Chinese coke oven workers. No influence was found in the association between urinary 1-OHP and other genetic polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this population.

Research paper thumbnail of Genome-wide association study identifies six susceptibility loci for glioma

Research paper thumbnail of Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population

Pharmacogenetics and Genomics, 2009

Research paper thumbnail of Genetic variations in EGF and EGFR and glioblastoma outcome

Neuro-Oncology, 2010

Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete ta... more Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94 -1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99 -1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

Research paper thumbnail of Molecular Cloning and Characterization of a Tobacco MAP Kinase Kinase That Interacts with SIPK

Molecular Plant-Microbe Interactions, 2000

A tobacco MAP kinase termed SIPK (salicylic acidinduced protein kinase) is activated in response ... more A tobacco MAP kinase termed SIPK (salicylic acidinduced protein kinase) is activated in response to a variety of stress signals, including pathogen attack and wounding (S. Zhang and D. F. Klessig, Proc. Natl. Acad. Sci. USA 95:7225-7230, 1998; S. Zhang and D. F. Klessig, Proc. Natl. Acad. Sci. USA 95:7433-7438, 1998). Using the yeast two-hybrid system, we have identified a gene encoding a

Research paper thumbnail of Effects of nitric oxide on growth of maize seedling leaves in the presence or absence of ultraviolet-B radiation

Journal of Plant Physiology, 2005

The leaves of maize seedlings were used to measure leaf biomass including leaf length, width and ... more The leaves of maize seedlings were used to measure leaf biomass including leaf length, width and weight, and to examine the relationship between nitric oxide (NO) synthase activity in microsomes and cytosol to the exo- and endo-beta-glucanase activity during growth. It was found that ultraviolet-B radiation (UV-B radiation) strongly induced nitric oxide synthase (NOS) activity but caused both a decrease of leaf biomass and exo- or endo-beta-glucanase activity. In contrast, the NOS inhibitor and NO donor largely decreased the activity of NOS in non-irradiated seedlings. The inhibitor also reduced exo- and endo-beta-glucanase activity and leaf biomass while the donor increased the enzyme activity and leaf biomass under normal conditions. Alternatively, under ultraviolet-B, the additional inhibitor of NOS and NO donor appeared to compromise the effects of ultraviolet-B on glucanase activity and leaf biomass, making the relationship between NOS activity and glucanase activity negatively correlated. This suggests that the changes of NOS activity showed a positive correlation to glucanase activity and leaf biomass in the absence of ultraviolet-B, but a negative correlation to ultraviolet-B irradiation and NO donor treatment alone. It is assumed that exo- and endogenous NO is responsible for the up-regulation of regular growth and development without ultraviolet-B. Under UV-B radiation, however, it might function as a signaling molecule of ultraviolet-B inhibiting leaf growth of maize seedlings to carry out stress-signaling transduction.

Research paper thumbnail of Allele Frequency Distribution at Seven Y-Chromosomal STR Loci Among Five Ethnic Groups from Northwest China

Journal of Forensic Sciences, 2005

Research paper thumbnail of Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 Genes Involved in the Double-Strand Break Repair Pathway Predict Glioblastoma Survival

Journal of Clinical Oncology, 2010

Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival.... more Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment.

Research paper thumbnail of Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics

Journal of Applied Genetics, 2011

Double minute chromosomes (DMs) are the cytogenetic hallmark of extra-chromosomal genomic amplifi... more Double minute chromosomes (DMs) are the cytogenetic hallmark of extra-chromosomal genomic amplification. The frequency of DMs in primary cancer and the cytogenetic features of DMs-positive primary cancer cases are largely unknown. To unravel these issues, we retrieved the Mitelman database and analyzed all DMs-positive primary cancerous karyotypes (787 karyotypes). The overall frequency of DMs is 1.4% (787 DMs-positive cases; total 54,398 cases). We found that DMs have the highest frequency in adrenal carcinoma (28.6%, topography) and neuroblastoma (31.7%, morphology). The frequencies of DMs in each tumor were much lower than in previous reports. The frequency of DMs in malignant cancers is significantly higher than in benign cancers, which confirms that DMs are malignant cytogenetic markers. DMs combined cytogenetic abnormalities are identified and sorted into two groups by principal component analysis (PCA), with one group containing -4, -5, -8, -9, -10, -13, -14, -15, -16, -17, -18, -20, -21, and -22, and the other containing -1p, -5q, +7, and +20. The prominent imbalance in DMs-positive cancer cases is chromosome loss. However, DMs-positive cancer cases, deriving from different morphologic cancers, cannot be clearly divided into subgroups. Our large database analysis provides novel knowledge of DMs and their combined cytogenetic abnormalities in primary cancer.

Research paper thumbnail of Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population

International Journal of Cancer, 2011

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic... more Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G1405C, G-634C) [odds ratio (OR) 5 1.29; 95% confidence interval (CI) 5 1.04-1.58; GC/CC vs. GG] and rs3025030 (OR 5 2.21; 95% CI 5 1.18-4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR 5 0.66; 95% CI 5 0.47-0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20-40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p 5 0.002, p corrected 5 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (p trend 5 8.4 3 10 25 ). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

Research paper thumbnail of Allergy and glioma risk: Test of association by genotype

International Journal of Cancer, 2011

between atopy and glioma risk these observations have been based on self-reporting of allergic co... more between atopy and glioma risk these observations have been based on self-reporting of allergic conditions raising the possibility that associations may be non-causal and arise as a consequence of bias, reverse causation or other artefacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analysed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13, and 17q21 that are associated with asthma or eczema risk at P < 5.0 x 10 -7 . The SNP rs7216389, which tags the 3' flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01-1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses.

Research paper thumbnail of XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital-based case-control study

International Journal of Cancer, 2009

In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in th... more In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype-based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancerfree controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR 5 1.44, 95% CI 5 1.15-1.80, p 5 0.001 and CT/TT versus CC: adjusted OR 5 1.66, 95% CI 5 1.12-2.46, p 5 0.013, respectively). Consistent with these results, XRCC3 haplotype ''GGCC'' containing rs861530 G allele and haplotype ''AGTC'' containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype ''AGCC'' (adjusted OR 5 1.35, 95% CI 5 1.14-1.58, p 5 0.000 and adjusted OR 5 1.67, 95% CI 5 1.11-2.52, p 5 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk. ' 2009 UICC