Tongzhang Zheng

Publications (173)786.78 Total impact

• Article: Single nucleotide polymorphisms in genes encoding for CC chemokines were not associated with the risk of Non-Hodgkin Lymphoma.

  Qiong Chen, Tongzhang Zheng, Qing Lan, Catherine Lerro, Nan Zhao, Qin Qin, Xiaobin Hu, Huang Huang, Jiaxin Liang, Theodore R Holford, Brian Leaderer, Peter Boyle, Stephen J Chanock, Nathaniel Rothman, Yawei Zhang
  [show abstract] [hide abstract]
  ABSTRACT: Abstract BACKGROUND: Chemokines play a pivotal role in immune regulation and response, and previous studies suggest an association between immune deficiency and Non-Hodgkin lymphoma (NHL). METHODS: We evaluated the association between NHL and polymorphisms in 18 genes (CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL18, CCL20, CCL24, CCL26, CCR1, CCR3, CCR4, CCR6, CCR7, CCR8 and CCR9) encoding for the CC chemokines using data from a population-based case-control study of NHL conducted in Connecticut women. RESULTS: CCR8 was associated with diffuse large B-cell lymphoma (DLBCL) (p = 0.012) and CCL13 was associated with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (p = 0.003) at gene level. After adjustment for multiple comparisons, none of the genes or SNPs were associated with risk of overall NHL or NHL subtypes. CONCLUSIONS: Our results suggest that the genes encoding for CC chemokines are not significantly associated with the risk of NHL, and further studies are needed to verify these findings. Impact: Our data indicate that CC chemokine genes were not associated with NHL risk.
  Cancer Epidemiology Biomarkers &amp Prevention 05/2013; · 4.12 Impact Factor
• Article: Polymorphisms in DNA repair pathway genes, body mass index, and risk of non-hodgkin lymphoma.

  Yingtai Chen, Tongzhang Zheng, Qing Lan, Christopher Kim, Qin Qin, Francine Foss, Xuezhong Chen, Theodore Holford, Brian Leaderer, Peter Boyle, Chengfeng Wang, Min Dai, Zhenjiang Liu, Shuangge Ma, Stephen J Chanock, Nathaniel Rothman, Yawei Zhang
  [show abstract] [hide abstract]
  ABSTRACT: We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in DNA repair pathway genes may modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared to those with BMI < 25, women with BMI ≥ 25 had significantly increased risk of NHL among women who carried BRCA1 (rs799917) CT/TT, ERCC2 (rs13181) AA, XRCC1 (rs1799782) CC, and WRN (rs1801195) GG genotypes, but no increase in NHL risk among women who carried BRCA1 CC, ERCC2 AC/CC, XRCC1 CT/TT, and WRN GT/TT genotypes. A significant interaction with BMI was only observed for WRN (rs1801195, P=0.004) for T-cell lymphoma and ERCC2 (rs13181, P=0.002) for diffuse large B-cell lymphoma. The results suggest that common genetic variation in DNA repair pathway genes may modify the association between BMI and NHL risk.
  American Journal of Hematology 04/2013; · 4.67 Impact Factor
• Article: Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes using Penalization

  Jin Liu, Jian Huang, Yawei Zhang, Qing Lan, Nathaniel Rothman, Tongzhang Zheng, Shuangge Ma
  [show abstract] [hide abstract]
  ABSTRACT: In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is a heterogeneous disease. Examining similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to better understanding of their connections and distinctions. Classic meta-analysis approaches analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis approaches, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with the prognosis of some subtypes but not the others. A compound penalization approach is developed to conduct gene-level analysis and identify genes that contain important SNPs associated with prognosis. The proposed approach has an intuitive formulation and can be realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed approach has satisfactory performance and outperforms meta-analysis using penalization. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed approach identifies genes different from alternative analysis and has reasonable prediction performance.
  04/2013;
• Article: A birth cohort analysis of the incidence of ascending and descending colon cancer in the United States, 1973-2008.

  Cairong Zhu, Bryan A Bassig, David Zaridze, Peter Boyle, Min Dai, Qian Li, Tongzhang Zheng
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVES: There is evidence indicating that the trends in colorectal cancer (CRC) incidence rates in the United States differ according to CRC subsites, including for ascending cancer which has shown a different pattern from the overall trends. We investigated the time trends for ascending and descending colon cancer in the United States by race and gender to identify the specific components that may account for the incidence trends. METHODS: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for 1973-2008, we conducted age-period-cohort modeling to evaluate birth cohort patterns and evaluate age-period-cohort effects on incidence trends of colon cancer over time. RESULTS: A clear birth cohort pattern was observed for both ascending and descending colon cancer, and the incidence rates of ascending colon cancer in the more recent birth cohorts were higher compared to earlier cohorts particularly for black males and females. This increase was most obvious in the younger age groups and appeared to accelerate, especially for black females. For descending colon cancer, the study suggested an increase in the birth cohort slope in the later birth cohorts for all gender and race groups, after a period of decline in earlier birth cohorts. CONCLUSION: The increase in incidence rates of both ascending and descending colon cancer in more recent birth cohorts for blacks suggests the need for targeted public health strategies to increase CRC screening. Further, additional etiological studies are warranted to evaluate factors responsible for the observed trends in more recent birth cohorts, including differences by subsites, race, and/or gender.
  Cancer Causes and Control 03/2013; · 2.88 Impact Factor
• Article: Global mercury and selenium concentrations in skin from free-ranging sperm whales (Physeter macrocephalus).

  Laura C Savery, David C Evers, Sandra S Wise, Carolyne Falank, James Wise, Christy Gianios, Iain Kerr, Roger Payne, W Douglas Thompson, Christopher Perkins, Tongzhang Zheng, Cairong Zhu, Lucille Benedict, John Pierce Wise
  [show abstract] [hide abstract]
  ABSTRACT: Pollution of the ocean by mercury (Hg) is a global concern. Hg persists, bioaccumulates and is toxic putting high trophic consumers at risk. The sperm whale (Physeter macrocephalus), is a sentinel of ocean health due to its wide distribution, longevity and high trophic level. Our aim was to survey Hg concentrations worldwide in the skin of free-ranging sperm whales considering region, gender and age. Samples were collected from 343 whales in 17 regions during the voyage of the research vessel, Odyssey, between 1999 and 2005. Skin was analyzed for total Hg and detected in all but three samples with a global mean of 2.5±0.1μgg-1 ranging from 0.1 to 16.0μgg-1. The Mediterranean Sea had the highest regional mean with 6.1μgg-1 followed by Australia with 3.5μgg-1. Considering gender, females and males did not have significantly different global Hg concentrations. The variation among regions for females was significantly different with highest levels in the Mediterranean and lowest in Sri Lanka; however, males were not significantly different among regions. Considering age in males, adults and subadults did not have significantly different Hg concentrations, and were not significantly different among regions. The toxic effects of these Hg concentrations are uncertain. Selenium (Se), an essential element, antagonizes Hg at equimolar amounts. We measured total Se concentrations and found detectable levels in all samples with a global mean of 33.1±1.1μgg-1 ranging from 2.5 to 179μgg-1. Se concentrations were found to be several fold higher than Hg concentrations with the average Se:Hg molar ratio being 59:1 and no correlation between the two elements. It is possible Hg is being detoxified in the skin by another mechanism. These data provide the first global analysis of Hg and Se concentrations in a free-ranging cetacean.
  Science of The Total Environment 03/2013; 450-451C:59-71. · 3.29 Impact Factor
• Article: Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis.

  Aaron E Hoffman, Ran Liu, Alan Fu, Tongzhang Zheng, Frank J Slack, Yong Zhu
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: miRNAs have been implicated in numerous tumorigenic pathways, and previous studies have associated miR-202 dysregulation with various cancer types, including follicular lymphoma. METHODS: The miR-202 targetome was identified by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip), and functional interactions among identified targets were investigated using the Ingenuity Pathway Analysis tool. We also performed a population-based genetic association study of a polymorphism within the miR-202 stem-loop sequence and risk of non-Hodgkin lymphoma. In vitro gain-of-function experiments were further conducted to elucidate the functional significance of the variant. RESULTS: 141 potential members of the miR-202 targetome were identified by a transcriptome-wide RIP-Chip assay. Functional interactions among identified targets suggested that miR-202 regulated genes are involved in biological pathways relevant for hematological function and cancer. Consistent with this, a genetic association analysis using human blood samples revealed a significant association between a germline mutation (rs12355840) in the miR-202 precursor sequence and follicular lymphoma (FL) risk. An in vitro functional assay further demonstrated that the variant allele resulted in diminished miR-202 levels, possibly by altering precursor processing efficiency. CONCLUSIONS: Taken together, our findings suggest that miR-202 is involved in follicular lymphomagenesis. Impact: These findings implicate miR-202 as a tumor suppressor in FL, and suggest that miR-202 expression may serve as a novel biomarker of FL risk.
  Cancer Epidemiology Biomarkers &amp Prevention 01/2013; · 4.12 Impact Factor
• Article: Subtype of dietary fat in relation to risk of Hodgkin lymphoma: a population-based case-control study in Connecticut and Massachusetts.

  Yongshun Gao, Qian Li, Bryan A Bassig, Ellen T Chang, Min Dai, Qin Qin, Yawei Zhang, Tongzhang Zheng
  [show abstract] [hide abstract]
  ABSTRACT: Few epidemiological studies have examined the relationship between dietary fat, which may affect immune function and risk of Hodgkin lymphoma (HL). The aim of this study was to test the hypothesis that high dietary intake of fat and specific subtypes of fat is associated with the risk of HL among 486 HL cases and 630 population-based controls recruited between 1997 and 2000 in Connecticut and Massachusetts. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) stratified by age and gender. Among younger adults, HL risk was significantly and positively associated with higher intake of saturated fat [ORs for increasing quartiles = 1.3, 1.8, and 2.1; p trend = 0.04] and negatively associated with higher intake of monounsaturated fat [ORs for increasing quartiles = 0.5, 0.5, and 0.4; p trend = 0.03), after adjustment for potential confounders including lifestyle and other dietary factors. The associations with saturated fat (ORs for increasing quartile = 2.4, 3.2, and 4.4; p trend < 0.01] and monounsaturated fat (ORs for increasing quartile = 0.3, 0.6, and 0.3; p trend = 0.04) were most apparent in younger women, whereas there was no significant association between intake of total fat or any type of fat and risk of HL in older females or younger or older males. These findings show that the associations between dietary fat and risk of HL may vary by gender and age and require confirmation in other populations.
  Cancer Causes and Control 01/2013; · 2.88 Impact Factor
• Article: Melatonin enhances DNA repair capacity possibly by affecting genes involved in DNA damage responsive pathways.

  Ran Liu, Alan Fu, Aaron E Hoffman, Tongzhang Zheng, Yong Zhu
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Melatonin, a hormone-like substance involved in the regulation of the circadian rhythm, has been demonstrated to protect cells against oxidative DNA damage and to inhibit tumorigenesis. RESULTS: In the current study, we investigated the effect of melatonin on DNA strand breaks using the alkaline DNA comet assay in breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. Our results demonstrated that cells pretreated with melatonin had significantly shorter Olive tail moments compared to non-melatonin treated cells upon mutagen (methyl methanesulfonate, MMS) exposure, indicating an increased DNA repair capacity after melatonin treatment. We further examined the genome-wide gene expression in melatonin pretreated MCF-7 cells upon carcinogen exposure and detected altered expression of many genes involved in multiple DNA damage responsive pathways. Genes exhibiting altered expression were further analyzed for functional interrelatedness using network- and pathway-based bioinformatics analysis. The top functional network was defined as having relevance for "DNA Replication, Recombination, and Repair, Gene Expression, [and] Cancer". CONCLUSIONS: These findings suggest that melatonin may enhance DNA repair capacity by affecting several key genes involved in DNA damage responsive pathways.
  BMC Cell Biology 01/2013; 14(1):1. · 2.59 Impact Factor
• Article: Body size and risk of Hodgkin's lymphoma by age and gender: a population-based case-control study in Connecticut and Massachusetts.

  Qian Li, Ellen T Chang, Bryan A Bassig, Min Dai, Qin Qin, Yongshun Gao, Yawei Zhang, Tongzhang Zheng
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS: A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS: These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.
  Cancer Causes and Control 12/2012; · 2.88 Impact Factor
• Article: Methylation alterations at imprinted genes detected among long-term shiftworkers.

  Daniel I Jacobs, Johnni Hansen, Alan Fu, Richard G Stevens, Anne Tjonneland, Ulla B Vogel, Tongzhang Zheng, Yong Zhu
  [show abstract] [hide abstract]
  ABSTRACT: Exposure to light at night through shiftwork has been linked to alterations in DNA methylation and increased risk of cancer development. Using an Illumina Infinium Methylation Assay, we analyzed methylation levels of 397 CpG sites in the promoter regions of 56 normally imprinted genes to investigate whether shiftwork is associated with alteration of methylation patterns. Methylation was significantly higher at 20 CpG sites and significantly lower at 30 CpG sites (P < 0.05) in 10 female long-term shiftworkers as compared to 10 female age- and folate intake-matched day workers. The strongest evidence for altered methylation patterns in shiftworkers was observed for DLX5, IGF2AS, and TP73 based on the magnitude of methylation change and consistency in the direction of change across multiple CpG sites, and consistent results were observed using quantitative DNA methylation analysis. We conclude that long-term shiftwork may alter methylation patterns at imprinted genes, which may be an important mechanism by which shiftwork has carcinogenic potential and warrants further investigation. © Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
  Environmental and Molecular Mutagenesis 11/2012; · 3.71 Impact Factor
• Article: Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium.

  Todd M Gibson, Karin E Smedby, Christine F Skibola, David W Hein, Susan L Slager, Silvia de Sanjosé, Claire M Vajdic, Yawei Zhang, Brian C-H Chiu, Sophia S Wang, [......], Katja Butterbach, Jacques Riby, Wendy Cozen, Yolanda Benavente, Casey Palmers, Elizabeth A Holly, Joshua N Sampson, Nathaniel Rothman, Bruce K Armstrong, Lindsay M Morton
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. METHODS: We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. RESULTS: Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. CONCLUSION: The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.
  Cancer Causes and Control 11/2012; · 2.88 Impact Factor
• Article: Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma.

  Wei Hu, Bryan A Bassig, Jun Xu, Tongzhang Zheng, Yawei Zhang, Sonja I Berndt, Theodore R Holford, H Dean Hosgood, Brian Leaderer, Meredith Yeager, Idan Menashe, Peter Boyle, Kaiyong Zou, Yong Zhu, Stephen Chanock, Qing Lan, Nathaniel Rothman
  [show abstract] [hide abstract]
  ABSTRACT: The pattern-recognition pathway plays an important role in infection recognition and immune responses, and previous studies have suggested an association between genetic variation in innate immunity genes and non-Hodgkin lymphoma (NHL). We evaluated NHL risk associated with genetic variation in pattern-recognition genes using data from a case-control study of NHL conducted in Connecticut women. Single nucleotide polymorphisms (SNPs) in 27 pattern-recognition genes were genotyped in 432 Caucasian incident NHL cases and 494 frequency-matched controls. Unconditional logistic regression was used to compute odds ratios (ORs) for NHL and common NHL subtypes in relation to individual SNPs and haplotypes. A gene-based analysis that adjusted for the number of tagSNPs genotyped in each gene showed a significant association with overall NHL for the MBP gene (P = 0.028), with the diffuse large B-cell lymphoma (DLBCL) subtype for the MASP2 gene (P = 0.011), and with the follicular lymphoma (FL) subtype for DEFB126 (P = 0.041). A SNP-based analysis showed that MBP rs8094402 was associated with decreased risks of overall NHL (allele risk OR = 0.72, P-trend = 0.0018), DLBCL (allele risk OR = 0.72, P-trend = 0.036), and FL (allele risk OR = 0.67, P-trend = 0.021), while MASP2 rs12711521 was associated with a decreased risk of DLBCL (allele risk OR = 0.57, P-trend = 0.0042). We also observed an increased risk of FL for DEFB126 rs6054706 (allele risk OR = 1.39, P-trend = 0.033). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NHL or specific NHL subtypes, but these preliminary findings require replication in larger studies. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
  Environmental and Molecular Mutagenesis 10/2012; · 3.71 Impact Factor
• Article: PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium.

  Alexandra Nieters, Lucia Conde, Susan L Slager, Angela Brooks-Wilson, Lindsay Morton, Danica R Skibola, Anne J Novak, Jacques Riby, Stephen M Ansell, Eran Halperin, [......], Claire M Vajdic, Andrew Grulich, Martyn T Smith, Paige M Bracci, Stephen J Chanock, Patricia Hartge, James R Cerhan, Sophia S Wang, Nathaniel Rothman, Christine F Skibola
  [show abstract] [hide abstract]
  ABSTRACT: Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms (SNPs) within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5,633 B-cell NHL cases and 7,034 controls from eight InterLymph studies. rs3789068 in the pro-apoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (OR=1.21, p-random=2.21x10(-11)) with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (OR=0.68, p-random=1.07x10(-9)) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.
  Blood 10/2012; · 9.90 Impact Factor
• Article: Integrative Analysis of Cancer Prognosis Data With Multiple Subtypes Using Regularized Gradient Descent.

  Shuangge Ma, Yawei Zhang, Jian Huang, Yuan Huang, Qing Lan, Nathaniel Rothman, Tongzhang Zheng
  [show abstract] [hide abstract]
  ABSTRACT: In cancer research, high-throughput profiling studies have been extensively conducted, searching for genes/single nucleotide polymorphisms (SNPs) associated with prognosis. Despite seemingly significant differences, different subtypes of the same cancer (or different types of cancers) may share common susceptibility genes. In this study, we analyze prognosis data on multiple subtypes of the same cancer but note that the proposed approach is directly applicable to the analysis of data on multiple types of cancers. We describe the genetic basis of multiple subtypes using the heterogeneity model that allows overlapping but different sets of susceptibility genes/SNPs for different subtypes. An accelerated failure time (AFT) model is adopted to describe prognosis. We develop a regularized gradient descent approach that conducts gene-level analysis and identifies genes that contain important SNPs associated with prognosis. The proposed approach belongs to the family of gradient descent approaches, is intuitively reasonable, and has affordable computational cost. Simulation study shows that when prognosis-associated SNPs are clustered in a small number of genes, the proposed approach outperforms alternatives with significantly more true positives and fewer false positives. We analyze an NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements and identify genes associated with the three major subtypes of NHL, namely, DLBCL, FL, and CLL/SLL. The proposed approach identifies genes different from using alternative approaches and has the best prediction performance.
  Genetic Epidemiology 07/2012; · 3.44 Impact Factor
• Article: Chapter 12: Yale lung cancer model.

  Theodore R Holford, Keita Ebisu, Lisa McKay, Cheongeun Oh, Tongzhang Zheng
  [show abstract] [hide abstract]
  ABSTRACT: The age-period-cohort model is known to provide an excellent description of the temporal trends in lung cancer incidence and mortality. This analytic approach is extended to include the contribution of carcinogenesis models for smoking. Usefulness of this strategy is that it offers a way to temporally calibrate a model that is fitted to population data and it can be readily adopted for the consideration of many different models. In addition, it provides diagnostics that can suggest temporal limitations of a particular carcinogenesis model in describing population rates. Alternative carcinogenesis models can be embedded within this framework. The two-stage clonal expansion model is implemented here. The model was used to estimate the impact of tobacco control after dissemination of knowledge of the harmful effects of cigarette smoking by comparing the observed number of lung cancer deaths to those expected if there had been no control compared to an ideal of complete control in 1965. Results indicate that 35.2% and 26.5% of lung cancer deaths that could have been avoided actually were for males and females, respectively.
  Risk Analysis 07/2012; 32 Suppl 1:S151-65. · 2.37 Impact Factor
• Article: Sexual functioning among testicular cancer survivors: a case-control study in the U.S.

  Christopher Kim, Katherine A McGlynn, Ruth McCorkle, Yonghong Li, Ralph L Erickson, Shuangge Ma, David W Niebuhr, Guangsheng Zhang, Yaqun Zhang, Yana Bai, Li Dai, Barry I Graubard, Tongzhang Zheng, Briseis Aschebrook-Kilfoy, Kathryn H Barry, Yawei Zhang
  [show abstract] [hide abstract]
  ABSTRACT: Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function. A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function. Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls. This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype.
  Journal of psychosomatic research 07/2012; 73(1):68-73. · 2.91 Impact Factor
• Article: Reply to offutt-powell et Al.

  Ni Li, Lin Yang, Lanwei Guo, Yawei Zhang, Ping Zhao, Tongzhang Zheng, Min Dai
  The Journal of Infectious Diseases 05/2012; 206(3):454-5. · 6.41 Impact Factor
• Article: Occupational solvent exposure, genetic variation in immune genes, and the risk for non-Hodgkin lymphoma.

  Qian Deng, Tongzhang Zheng, Qing Lan, Yajia Lan, Theodore Holford, Yingtai Chen, Min Dai, Brian Leaderer, Peter Boyle, Stephen J Chanock, Nathaniel Rothman, Yawei Zhang
  [show abstract] [hide abstract]
  ABSTRACT: Solvent exposure has been inconsistently linked to the risk for non-Hodgkin lymphoma (NHL). The aim of this study was to determine whether the association is modified by genetic variation in immune genes. A population-based case-control study involving 601 incident cases of NHL and 717 controls was carried out in 1996-2000 among women from Connecticut. Thirty single nucleotide polymorphisms in 17 immune genes were examined in relation to the associations between exposure to various solvents and the risk for NHL. The study found that polymorphism in interleukin 10 (IL10; rs1800890) modified the association between occupational exposure to organic solvents and the risk for diffuse large B-cell lymphoma (Pfor interaction=0.0058). The results remained statistically significant after adjustment for false discovery rate. Compared with women who were never occupationally exposed to any organic solvents, women who were exposed to organic solvents at least once had a significantly increased risk for diffuse large B-cell lymphoma if they carried the IL10 (rs1800890) TT genotype (odds ratio=3.31, 95% confidence interval: 1.80-6.08), but not if they carried the AT/AA genotype (odds ratio=1.14, 95% confidence interval: 0.72-1.79). No significant interactions were observed for other immune gene single nucleotide polymorphisms and various solvents in relation to NHL overall and its major subtypes. The study provided preliminary evidence supporting a role of immune gene variations in modifying the association between occupational solvent exposure and the risk for NHL.
  European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 05/2012; · 2.21 Impact Factor
• Article: Genetic polymorphisms in IL10RA and TNF modify the association between blood transfusion and risk of non-Hodgkin lymphoma.

  Xiaofeng Bi, Tongzhang Zheng, Qing Lan, Zhijian Xu, Yingtai Chen, Gongjian Zhu, Francine Foss, Christopher Kim, Min Dai, Ping Zhao, Theodore Holford, Brian Leaderer, Peter Boyle, Qian Deng, Stephen J Chanock, Nathaniel Rothman, Yawei Zhang
  [show abstract] [hide abstract]
  ABSTRACT: We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes may modify the association between blood transfusion and risk of non-Hodgkin lymphoma (NHL). Compared with women without blood transfusion, women with a history of transfusion had an increased risk of NHL if they carried IL10RA (rs9610) GG genotype [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.1-3.2] or TNF (rs1800629) AG/AA genotypes (OR = 1.6, 95% CI: 0.9-2.7). We also found women with a history of transfusion had a decreased risk of NHL if they carried IL10RA (rs9610) AG/AA genotypes (OR = 0.6, 95% CI: 0.4-0.9) or TNF (rs1800629) GG genotype (OR = 0.7, 95% CI: 0.5-1.0). A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. Statistically significant interactions with blood transfusion were observed for IL10RA (rs9610) (P(forinteraction) = 0.003) and TNF (rs1800629) (P(forinteraction) = 0.012) for NHL overall and IL10RA (rs9610) (P(forinteraction) = 0.001) and TNF (rs1800629) (P(forinteraction) = 0.019) for B-cell lymphoma. The results suggest that genetic polymorphisms in TNF and IL10RA genes may modify the association between blood transfusion and NHL risk.
  American Journal of Hematology 04/2012; 87(8):766-9. · 4.67 Impact Factor
• Article: Methyl bromide exposure and cancer risk in the Agricultural Health Study.

  Kathryn Hughes Barry, Stella Koutros, Jay H Lubin, Joseph B Coble, Francesco Barone-Adesi, Laura E Beane Freeman, Dale P Sandler, Jane A Hoppin, Xiaomei Ma, Tongzhang Zheng, Michael C R Alavanja
  [show abstract] [hide abstract]
  ABSTRACT: Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects. We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score. A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR = 1.42; 95 % CI, 0.51-3.95 and RR = 3.13; 95 % CI, 1.25-7.80 for low and high use compared with no use; p (trend) = 0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance. Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.
  Cancer Causes and Control 04/2012; 23(6):807-18. · 2.88 Impact Factor