Yuanqing Ye

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (115)1010.61 Total impact

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    ABSTRACT: Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6,911 cases and 11,814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P<1×10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15,058 cases and 286,270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P=2.19×10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P=3.3×10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5,551 bladder cancer cases and 10,242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region - the first signal is marked by rs6104690 and the second signal is marked by two moderately correlated SNPs (r(2)=0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared to non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P<0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
    No preview · Article · Jan 2016 · Human Molecular Genetics

  • No preview · Article · Dec 2015 · International Journal of Epidemiology
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    ABSTRACT: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
    Full-text · Article · Oct 2015 · JNCI Journal of the National Cancer Institute

  • No preview · Article · Aug 2015 · Cancer Research
  • Liren Zhang · Jack A. Roth · Jie Lian · Yuanqing Ye · Jian Gu · Xifeng Wu

    No preview · Article · Aug 2015 · Cancer Research
  • Xia Pu · Jaffer A. Ajani · Jian Gu · Xiangjun Gu · Yuanqing Ye · Xifeng Wu

    No preview · Article · Aug 2015 · Cancer Research

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: Background: Meat-cooking mutagens may be associated with renal cell carcinoma (RCC) risk. In the current study, the authors examined associations between meat-cooking mutagens, genetic susceptibility variants, and risk of RCC. Methods: The authors used 659 newly diagnosed RCC cases and 699 healthy controls to investigate the association between dietary intake of meat-cooking mutagens and RCC. They examined whether associations varied by risk factors for RCC and genetic susceptibility variants previously identified from genome-wide association studies. Odds ratios and 95% confidence intervals were estimated using tertiles of intake of dietary polycyclic aromatic hydrocarbons/heterocyclic amines. Results: Dietary intake of the mutagenic compounds 2-amino-3,8-dimethylimidazo-(4,5-f) quinoxaline (MeIQx) and 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) were found to be significantly associated with an increased risk of RCC (odds ratios across tertiles: 1.00 [referent], 1.28 [95% confidence interval, 0.94-1.74], and 1.95 [95% confidence interval, 1.43-2.66] [P for trend <.001], respectively; and 1.00 [referent], 1.41 [95% confidence interval, 1.04-1.90], and 1.54 [95% confidence interval, 1.14-2.07] [P for trend =.02], respectively). The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06). Conclusions: The intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions. Cancer 2015. © 2015 American Cancer Society.
    No preview · Article · Aug 2015 · Cancer Research

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: Post-operative pulmonary complications are the most common morbidity associated with lung resection in non-small cell lung cancer (NSCLC) patients. The TNF/TRAF2/ASK1/p38 kinase pathway is activated by stress stimuli and inflammatory signals. We hypothesized that genetic polymorphisms within this pathway may contribute to risk of complications. In this case-only study, we genotyped 173 germline genetic variants in a discovery population of 264 NSCLC patients who underwent a lobectomy followed by genotyping of the top variants in a replication population of 264 patients. Complications data was obtained from a prospective database at MD Anderson. MAP2K4:rs12452497 was significantly associated with a decreased risk in both phases, resulting in a 40% reduction in the pooled population (95% CI:0.43-0.83, P = 0.0018). In total, seven variants were significant for risk in the pooled analysis. Gene-based analysis supported the involvement of TRAF2, MAP2K4, and MAP3K5 as mediating complications risk and a highly significant trend was identified between the number of risk genotypes and complications risk (P = 1.63 × 10(-8)). An inverse relationship was observed between association with clinical outcomes and complications for two variants. These results implicate the TNF/TRAF2/ASK1/p38 kinase pathway in modulating risk of pulmonary complications following lobectomy and may be useful biomarkers to identify patients at high risk.
    Preview · Article · Jul 2015 · Scientific Reports
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    ABSTRACT: The genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of developing bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers leading us to believe this pathway may play a vital role in bladder cancer development. A total of 230 SNPS in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. Twenty SNPs were nominally significant for risk. Individuals with two variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer (OR=0.76, 95% CI: 0.58-0.99, P=0.039) in the recessive model in the initial analysis and was also validated using the bladder GWAS chip (OR=0.51, 95% CI: 0.27-1.00, P=0.049) (P value for combined analysis: P=0.007). Together, these findings implicate variants in the Wnt/β-catenin stem-cell pathway as playing a role in bladder cancer etiology. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · The Journal of urology
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    ABSTRACT: We aimed to identify new serum biomarkers of esophageal adenocarcinoma (EAC). We performed metabolomic analyses of serum samples from 30 patients with histologically confirmed EAC (cases) from The University of Texas MD Anderson Cancer Center and 30 patients without EAC (controls). We identified metabolites whose levels differed significantly between cases and controls and validated those with the greatest difference in an analysis of 321 EAC cases and 331 controls. We generated a metabolite risk score (MRS) for the metabolites. The levels of 64 metabolites differed significantly between EAC cases and controls. The metabolites with the greatest difference were: amino acid L-proline (LP), ketone body 3-hydroxybutyrate (BHBA), and carbohydrate D-mannose (DM) different; these differences were confirmed in the validation set. Cases had lower mean levels of LP that controls (22.78±6.79 ug/ml vs 28.24±8.64 ug/ml; P<.001) and higher levels of BHBA (18.06±17.84 ug/ml vs 7.73±9.92 ug/ml; P<.001) and DM (9.87±4.28 ug/ml vs 6.28 ±3.61 ug/ml; P<.001). Levels of DM were significant higher in patients with late-stage EAC than early-stage EAC (10.61±4.79 ug/ml vs 8.97±3.36 ug/mL; P=.005). Higher levels of LP were associated with a significant decreased in risk of EAC (odds ratio [OR] =0.26; 95% confidence interval [CI], 0.18-0.38). A significant increase in risk of EAC was associated with higher levels of BHBA (OR=4.05; 95% CI, 2.84-5.78) and DM (OR=7.04; 95% CI, 4.79-10.34). Levels of all 3 metabolites associated with EAC risk in quartile analyses; the level of risk conferred by the metabolites increased with smoking status and body mass index. Individuals with a high MRS had a significant (7.76-fold) increase in risk of EAC vs those with low a MRS. Smokers with a high MRS had the greatest risk of EAC (OR=20.26; 95% CI,11.19-36.68), compared with never smokers with a low MRS. Based On A Case Vs Control Metabolic Profile analysis, levels of LP, BHBA and DM are associated with risk of EAC. These markers might be used as prognostic factors for patients with EAC. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
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    ABSTRACT: Mitochondrial DNA (mtDNA) content has been shown to be associated with cancer susceptibility. We identified 926 bladder cancer patients and compared these to 926 healthy-controls frequency matched on age, gender, and ethnicity. Patients diagnosed with bladder cancer had significantly decreased mtDNA content when compared to control subjects (median: 0.98 vs. 1.04, p<0.001). Low mtDNA content (ie, less than the median in control subjects) was associated with a statistically significant increased risk of bladder cancer, when compared with high mtDNA content (Odds Ratio (OR) = 1.37, 95% CI = 1.13 to 1.66, p<0.001). In a trend analysis, a statistically significant dose-response relationship was detected between lower mtDNA content and increasing risk of bladder cancer (P for trend <0.001). When stratified by host characteristics, advanced age (>65 years), male/female sex and positive smoking history were all significantly associated with low mtDNA content and increased risk of bladder cancer. We identified two unique mtDNA polymorphisms significantly associated with risk of bladder cancer: mitot10464c (OR=1.39 95%CI: 1.00-1.93, p=0.048) and mitoa4918g (OR=1.40, 95% CI: 1.00-1.95, p=0.049). Analysis of the joint effect of low mtDNA content and unfavorable mtDNA polymorphisms revealed a 2.5 fold increased risk of bladder cancer (OR=2.50, 95% CI: 1.60-3.94, p<0.001). Significant interaction was observed between mitoa4918g and mtDNA content (p for interaction = 0.028). Low mtDNA content was associated with increased risk of bladder cancer and we identified new susceptibility mtDNA alleles associated with increased risk that require further investigation into the biological underpinnings of bladder carcinogenesis. Copyright © 2015, American Association for Cancer Research.
    Preview · Article · Apr 2015 · Cancer Prevention Research
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    ABSTRACT: Glutathione (GSH) is an important molecule involved in cell detoxification and antioxidation and may affect cancer development or outcome. We hypothesized that genetic variation in the GSH pathway might influence the clinical outcome of patients who have non-muscle invasive bladder cancer (NMIBC). A total of 114 single nucleotide polymorphisms (SNPs) in 21 GSH pathway genes were genotyped in 414 NMIBC patients treated with transurethral resection alone (TUR) and both TUR and intravesical bacillus Calmette-Guérin instillation (BCG) therapy. The effect of each SNP on time to recurrence was estimated using the multivariate Cox proportional hazards model. Cumulative effect and survival tree analyses were performed to determine the joint effects of unfavorable genotypes and gene-gene interactions on bladder cancer prognosis. Seven SNPs showed significant associations with cancer recurrence in the TUR group and 15 SNPs showed significant associations with recurrence in the BCG group. The most significant SNP in the TUR group was rs3746162 in GPX4, whose variant genotype conferred a 5.4-fold increased risk of recurrence compared with wild-type (hazard ratio [HR] = 5.43, 95 % confidence interval [CI] = 2.19-13.46), whereas the most significant SNP in the BCG group was rs7265992 in GSS (HR 3.43, 95 % CI 1.56-7.56). The risk of recurrence increased with the number of unfavorable genotypes in both groups. Within treatment group, stratified analyses by tumor grade also indicated predictive variants. Genetic variants in GSH pathway may influence cancer recurrence in NMIBC patients receiving curative treatment.
    Preview · Article · Apr 2015 · Annals of Surgical Oncology
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    ABSTRACT: Hispanic Americans comprise the largest and fastest-growing ethnic minority in the USA. In Houston, Texas, 44% of the population is of Hispanic descent, with the majority being Mexican Americans (78%). This population is under-represented in health-related research despite their high prevalence of obesity and diabetes, which may predispose them to cancer and other chronic conditions. Recognizing the need for a greater research effort into the health risks of Hispanic Americans, the population-based Mexican American (Mano a Mano) Cohort study was launched in 2001. This is an open cohort with enrolment ongoing to 2019, and as of 30 June 2014, 23 606 adult participants from over 16 600 households were enrolled. Bilingual interviewers elicit information in person on demographics, acculturation, lifestyle, occupation, medical history, family cancer history, self-reported and measured height and weight, and other exposures. Urine, blood and saliva samples have been collected at baseline from 43%, 56% and 63% of participants, respectively. DNA samples are available for about 90% of participants. Incident cancers and other chronic diseases are ascertained through annual telephone re-contact and linkage to the Texas Cancer Registry and/or medical records. Molecular data such as genetic ancestry markers, blood telomere length and HbA1c, a marker of impaired glucose tolerance, are available for a substantial proportion of the participants. Data access is provided on request [manoamano@mdanderson.org]. For further information please visit [www.mano-mano.us]. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    Full-text · Article · Mar 2015 · International Journal of Epidemiology
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    ABSTRACT: We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLA-DQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immune-related pathway and genes in the etiology of RCC.
    Full-text · Article · Feb 2015 · Oncotarget
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    ABSTRACT: Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
    Full-text · Article · Jan 2015 · Nature Communications
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    ABSTRACT: Liver function tests (LFTs) have been reported as independent predictors of non-liver disease-related morbidity and mortality in general population and cancer patients. In this study, we evaluated the relationship between pretreatment serum LFTs and overall survival (OS) in non-metastatic Caucasian breast cancer patients. Seven LFTs, including albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, and total protein, were measured in pretreatment serum from 2,425 female Caucasian patients with newly diagnosed, histologically confirmed non-metastatic invasive breast cancer. Multivariate Cox model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the association of individual LFTs with 5-year OS while adjusting for age, smoking status, pathological characteristics and treatment regimen. We found that serum albumin, LDH, and total bilirubin were significantly associated with 5-year OS in multivariate Cox analyses. Patients with higher albumin level exhibited 45% reduced risk of death (HR=0.55, 95% CI, 0.40-0.75) compared to those with lower albumin level. Patients with higher total bilirubin level had a nearly 40% reduction in the risk of death (HR=0.62, 95% CI, 0.45-0.85) and patients with higher LDH levels had a 1.42-fold increased risk of death (HR=1.42, 95% CI, 1.08-1.88). Furthermore, cumulative analysis showed a significant dose-response trend of significantly increasing risk of death with increasing number of unfavorable LFT levels. Our result highlighted the potential of using pretreatment serum levels of albumin, LDH and total bilirubin as prognostic factors for overall survival in patients with non-metastatic breast cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Dec 2014 · Carcinogenesis
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    ABSTRACT: BACKGROUND In the current study we present a validated miRNA signature to predict pathologic complete response (pCR) to neoadjuvant chemoradiation in esophageal adenocarcinoma.METHODS Three patient cohorts (discovery, n = 10; model, n = 43; and validation, n = 65) with locally advanced esophageal adenocarcinoma were analyzed. In the discovery cohort 754 miRNAs were examined in pretreatment tumor biopsy specimens using a TaqMan array. Of these, the 44 most significantly altered between tumors with pCR and non-pCR were examined in an additional 43 tumors using a Fluidigm 48.48 array. The 4 miRNAs (mir-505*, mir-99b, mir-451, and mir-145*) significantly predicting pCR in both cohorts were examined in an additional validation cohort (n = 65) using an Illumina array. These 4 miRNAs were used to generate an miRNA expression profile (MEP) score.RESULTSThe 4 miRNAs profiled are highly significantly associated with pCR in the model cohort (Ptrend = .008), the validation cohort (Ptrend = .025), and the combined cohort (Ptrend = 4.6 × 10−4). The receiver-operator characteristic areas under the curves (AUCs) for the MEP score were 0.78 for the model cohort, 0.71 for the validation cohort, and 0.72 for the combined cohort. When combined with clinical variables, the MEP score AUCs increased to 0.89, 0.77, and 0.81, respectively Estimates from logistic regression based on the MEP were determined and used to generate a probability of pCR plot, which identifies a group of patients with very high (≥80%) and very low (≤10%) probability of pCR.CONCLUSIONS The MEP score provides a validated means of predicting pCR to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma that is robust across several analysis platforms. Cancer 2014. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    Full-text · Article · Dec 2014 · Cancer
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    ABSTRACT: Background: Depression is associated with an increased risk of mortality in cancer patients; it has been hypothesized that depression-associated alterations in cell aging mechanisms in particular, the telomere/telomerase maintenance system, may underlie this increased risk. We evaluated the association of depressive symptoms and telomere length to mortality and recurrence/progression in 464 bladder cancer patients. Methods: We used the CES-D and SCID to assess current depressive symptoms and lifetime MDD, respectively, and telomere length was assessed from peripheral blood lymphocytes. Multivariate Cox regression was used to assess the association of depression, and telomere length to outcomes and the joint effect of both. Kaplan-Meier plots and log rank tests were used to compare survival time of subgroups by depression variables and telomere length. Results: Patients with depressive symptoms (CES-D ≥16) had a 1.83-fold (95%CI= 1.08 to 3.08, P=0.024) increased risk of mortality compared to patients without depressive symptoms (CES-D < 16) and shorter disease-free survival time (P=0.004). Patients with both depressive symptoms and lifetime history of MDD were at 4.88-fold (95%CI=1.40 to 16.99; P=0.013) increased risk compared to patients with neither condition. Compared to patients without depressive symptoms and long telomere length, patients with depressive symptoms and short telomeres exhibited a 4-fold increased risk of mortality (HR=3.96, 95% CI=1.86 to 8.41, P=0.0003) and significantly shorter disease-free survival time (P<0.001). Conclusion: Short telomere length and depressive symptoms are associated with bladder cancer mortality individually and jointly. Impact: Further investigation of interventions that impact depression and telomere length may be warranted in cancer patients. Copyright © 2014, American Association for Cancer Research.
    Full-text · Article · Nov 2014 · Cancer Epidemiology Biomarkers & Prevention