Carcinogenesis, Biomarkers & Epidemiology Program

Overview | Leaders | Members | Research | Publications | Activities

 

Research Portfolio

Recent accomplishments of the CBE Program include:

  • Dr. Chung elucidated the roles of cyclic DNA adducts from lipid peroxidation in the apoptosis induced by omega-3 versus omega-6 fatty acids in human colon carcinogenesis (Chung et al. 2003).
  • Proteomic patterns identified as promising markers for early liver cancer detection, as reported by Drs. Goldman and Ressom, in collaboration with Dr. Seillier-Moiseiwitsch for testing in Dr. Loffredo's case-control study of hepatocellular carcinoma (Orvisky et al. 2006; Goldman et al. 2007; Ressom et al. 2006, 2007, 2008).
  • Previously unknown genetic diversity of hepatitis C virus in Egypt (which has the world's highest population prevalence of HCV) was discovered, and found to be associated with evidence of accelerated liver carcinogenesis by Dr. Loffredo and colleagues (Abdel-Hamid et al. 2007).

View a full list of accomplishments from 2002 to 2008

Additionally, there are many ongoing studies:

 

Mechanistic and pathway studies in lung, colon, and oral cancers.
Investigators: Chung, Shields, Goldman

In this section we summarize CBE Program research on the role of exogenous and endogenous exposures in causing DNA damage and how this damage is repaired. This work complements, and is synergistic with, the research on human genotypic variation in the same pathways that are actively being investigated in human studies by other CBE Program members.

Dr. Chung's laboratory is studying cyclic DNA adducts caused by aldehydes (enals) generated by lipid peroxidation of w-3 and w-6 fatty acids (Chung et al. 2003), and he has also developed methods for identifying DNA adducts from crotonaldehyde and acrolein (carcinogens of increasing concern as constituents of air pollution and cigarette smoke; they are also products of endogenous lipid peroxidation). Dr. Chung has competitively renewed an NCI R01 grant in which he and Dr. Roy are addressing the question why w-3 and w-6 fatty acids with subtle structural variations show opposite effects toward colon cancer development. Another focus of the Chung laboratory is to discover compounds, through mechanistic studies that could be used as potential cancer chemopreventive agents. He has identified a number of promising active cancer-preventive compounds in the isothiocyanate (ITC) family derived from cruciferous vegetables that may be effective in decreasing lung and colon cancer risk (Conaway et al, 2005; Yang et al, 2005). An R01 grant, "Mechanisms of Chemoprevention by Isothiocyanates," was awarded in 2004 to support this work: its goal is to identify the protein targets of apoptosis induced by ITCs using 2-D gel electrophoresis and mass spectroscopy (Mi et al., 2008). The human component of this work has extended to the Shanghai Cohort Study and several case-control studies; the roles of different glutathione S-transferases (GST) genotypes in the protection against lung cancer by dietary isothiocyanates were defined (London et al. 2000; Fowke et al, 2003; Moy et al, 2008). These data were used to support an NCI funded R01 for a clinical trial, with Dr. Chung as PI, to investigate the effects of GSTM1 and GSTT1 genotypes on the metabolism of PEITC after ingestion of watercress juice. Drs. Shields and Goldman also contribute to this project by performing GST genotyping and comet assays.

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Tobacco addiction and harm
Investigators: Rice, Kellar, Xiao, Shields, Seillier-Moiseiwitsch, Johnson, Ressom, Wang, Higby (Arista Laboratories), Clarke, Zheng, Makambe, Marian

CBE Program members Drs. Rice, Kellar, Xiao and Shields are studying basic mechanisms for tobacco-related carcinogenesis and nicotine addiction. These are complementary to other projects that are ongoing in humans (see description of the NCI N01 funded tobacco project below, which developed in part from ongoing collaborative work by this group). In the following narrative, we highlight the accomplishments in this area and summarize applications of this work to populations.

Drs. Kellar and Xiao's studies are focused on nicotinic receptors (nAChRs) in the central nervous system (CNS) and autonomic nervous system. These receptors are pentameric ligand-gated cation channels assembled from among nine α and three β subunits. One of the unusual properties of α4β2 nAChRs in the brain is that they are up-regulated by exposure to nicotine. This increase in nAChRs is seen in rats and mice administered nicotine, as well as in autopsied brains from smokers. To study this, Drs. Kellar and Dr. Xiao have developed stable human cell lines that heterologously express different nAChR subtypes (Xiao & Kellar, 2004). These investigators also have been developing selective inhibitors of nicotinic receptors to better understand the role of these receptors in response to nicotine and other agonists (Xiaoet al., 2004, Zhouet al., 2006).

Drs. Shields, Kellar, Rice, Xiao, Seillier-Moiseiwitsch, Johnson, Ressom and Wang have been collaborating to understand the role of nicotine and nicotinic receptors in human cells and the effect of varied nicotine in tobacco products (funded by an NCI N01 contract and an RO1). Commercially available low-nicotine and nicotine-free cigarettes marketed to smokers seeking to reduce their nicotine intake were tested in a variety of experiments to identify changes in smoke yields and toxicity. Sixty constituents in mainstream cigarette smoke were analyzed, in collaboration with Dr. Richard Higby at Arista Laboratories. Nicotine, some tobacco-specific nitrosamines, aldehydes and volatiles were reduced in these cigarettes, while aromatic amines were higher. Toxicology studies demonstrated the measurable role for nicotine within cigarette smoke condensate and indicated that these cigarettes are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells (Chen, et al, 2008). Studies are now underway, funded by an NCI RO1 to Dr. Rice, to determine the effects of adding nicotine back to nicotine-free cigarettes and also the effects of nicotine free cigarettes, compared to conventional cigarettes, on various in vitro and in vivo toxicological endpoints.

Drs. Shields, Kellar, Seillier-Moiseiwitsch, Wang, and Clarke have been seeking to identify potential biomarkers for the effects of cigarette smoke and nicotine exposure, and the individual variation of response, by using cultured lymphocytes exposed to nicotine and cigarette smoke condensate of low nicotine and nicotine-free cigarettes, as well as uncultured lymphocytes from smokers (heavy and light) and nonsmokers. Using the Affymetrix HG-U133A GeneChips to measure global gene expression, genes encoding for enzymes that mediate xenobiotic toxicity were most notably increased, and were transcriptionally upregulated through the Nrf2 and AhR signaling pathways. Gene ontology and biological pathway analyses revealed that the modulated genes were mainly involved in oxidative stress-response, inflammation and immune response, apoptosis, cell cycle and tumorigenesis. For nicotine effects, 65 overlapping genes were identified in cultured lymphocytes and and lymphocytes from blood, and included genes encoding transcription factors, cytoskeleton and matrix proteins, especially genes involved in immune response. The data from these studies demonstrate that cigarette smoke causes different gene expression signatures, and that nicotine effects are measurable within the complex exposure of cigarette smoke (Chen et al 2009, submitted; Chen et al 2009, in preparation).

The above data, in addition to pilot funding from the Lombardi, led to the award of a multi-institution, peer-reviewed NO1 contract from the NCI to develop methods to study new tobacco products, including both cigrarettes and smokeless tobacco. The Lombardi, in addition to Dr. Shields being the PI, is principally responsible to develop toxicological methods and test new tobacco products, among other activities. This work is done in collaboration by Drs. Shields, Zheng, Rice, Johnson, Makambe, and Marian. This work specifically is developing new methods for the generation of cigarette smoke condensate using smoking machines and mimicking human smoking behavior, the use of the COMET and gap junction intercellular communication, and various genotoxicity and apoptosis assays. Also, extensive web-based research tools are being developed, as well as numerous critical reviews for methods of studying tobacco products (e.g., ranging from toxicology to surveillance and risk assessment). The Tobacco Products Assessment Consortia has established a website at: www.tobaccoscience.org.

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Breast cancer studies
Investigators: Shields, Furth, Cavalli, Haddad

Dr. Shields and Furth have been awarded a DOD Synergy Grant to conduct experimental animal and human studies following the observation by Dr. Furth that BRCA1 negatively impacts on TGFb for mammary carcinogenesis. Animal studies are being conducted, and Dr. Shields is conducting parallel studies examining TGFb and related proteins and receptor expression in normal breast tissues collected from reduction mammoplasty in women with no history of cancer.

Dr. Luciane Cavalli, in collaboration with Dr. Haddad, focuses on the mechanisms of amplification and effects of the BP1 gene in breast cancer, and its correlation with progression and invasion. This gene maps to chromosome 17q21, a hot spot location in breast cancer, and has been found to be amplified and over-expressed in these tumors. She is evaluating samples of "triple negative" breast cancer (i.e. negative for ER, PR, and Her2/Neu), as well as paired samples of primary tumors and corresponding metastatic sentinel lymph nodes.

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Proteomics research to develop biomarkers for prostate, head and neck, and liver cancer
Investigators: Goldman, Ressom, Loffredo, Seillier-Moiseiwitsch, Adali (University of Maryland-Baltimore County), Roy (University of Maryland-Baltimore County), Bebu

Drs. Goldman and Ressom are developing new bio-analytical methods to use proteomic profiles as diagnostic and prognostic biomarkers of cancer, particularly primary liver cancer, as described below, but also for prostate cancer and head and neck squamous cell carcinomas (Saha et al 2008). They developed bioinformatics methods for analysis of serum proteomic profiles (Ressom et al, 2005, 2006, 2007, 2008) and new methods for enriching serum by denaturing ultrafiltration, which enables an efficient profiling and identification of peptides up to 5 kDa (Orvisky et al, 2006). Dr. Ressom computational method combined support vector machines with swarm intelligence methods for optimal biomarker selection (Ressom et al, 2005). Application of these methods to 150 serum samples of patients with hepatocellular carcinoma (HCC) and matched controls with chronic hepatitis C viral infection (from Dr. Loffredo's study population) identified six peptides that classify HCC with 100% sensitivity and 92% specificity (Goldman et al 2007). The same specimen set was used to develop glycan biomarkers. This work led to an NCI-funded R01 (PI: Goldman) as a continuing collaboration with Dr. Ressom and Dr. Loffredo to study subjects enrolled in a case-control study in Egypt, leveraging Dr. Loffredo's longstanding R01 (1999-2010). The ultimate goal of this body of research is to establish a multiplex MALDI-TOF isotope dilution assay for early detection of HCC.

Dr. Seillier-Moiseiwitsch's research has focused on the development of analytical protocols for two-dimensional gel images and LC-MS data. The novel methodology uses (i) image analysis techniques to remove noise, (ii) quadratic programming combined with a powerful optimization procedure to align whole images (Potra et al. 2006) and (iii) a multiple-testing formulation in the wavelet domain for detecting significant differences in protein expression across groups of images. She developed a highly automated method for cleaning 2D-PAGE images and detecting spots. To detect differentially expressed proteins, together with Drs. Adali and Roy (University of Maryland-Baltimore County), she implemented spatial independent component analysis (ICA). ICA proved to be much faster than ANOVA and unlike ANOVA, it does not depend on any threshold. ICA in the wavelet domain offers increase in speed and also, better performance for misaligned gels as compared to the spatial domain (Correa et al., 2006; Safavi et al., 2008). Separately, Drs. Bebu and Seillier-Moiseiwitsch have worked on improving the Robust Multichip Average (RMA) methodology for pre-processing Affymetrix microarray chips. The assumption is that the noise is Gaussian, but, while the method uses only perfect matches to correct for background noise, their procedure (called semi-RMA) provides a solution of a convolution equation treated as a quadratic programming problem with constraints (Bebu et al, 2007, 2008).

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Development and validation of genetic-based biomarkers
Investigators: Zheng, Loffredo, Shields, Adams-Campbell, Haddad, Willey, Blancato, Byrne, Freedman, Seillier-Moiseiwitsc, Mamambe, Dickson, Furth, Sidawy, Johnson, Singh

Multiple members of the CBE Program have been developing new phenotypic markers reflecting complex heritable traits for cancer susceptibility. It should be noted that phenotypic markers are conceptually better predictors of risk because they represent complex genetic traits, but are usually technically difficult to implement in population studies (not amenable to high throughput), so that they are usually applied in small, focused studies. Nonetheless, as the following studies will show, these studies have been sufficient to demonstrate statistically significant risk factors for cancer.

Dr. Yun-Ling Zheng, working with Drs. Loffredo, Shields, and Adams-Campbell has developed and assessed phenotypic assays for DNA repair using the mutagen sensitivity assay, and separately, has developed assays to assess the G2/M checkpoint arrest and telomerase activity. The development of these assays has led to the application in several humans studies, as published, and detailed below under Aim 3 (Zheng et al, 2003)(Zheng et al, 2005)(Natarjan 2006). Other genotypic markers have been assessed in relation to smoking. The NO1 contract to develop new biomarkers for tobacco smoke and smokeless tobacco exposure is allowing for the investigation of urine mutagenicity, the Comet assay and sister chromatid exchanges. Also, funded in part by this contract, Dr. Shields and coworkers developed methods for the detection of mitochondrial DNA mutations in human cells, which correlate with levels of smoking (Tan, 2008).

Dr. Bassem Haddad has had longstanding research interests in developing better cytogenetic screening methodologies to detect premalignant breast lesions and early stage breast cancer in high-risk women. In a study currently funded by the Avon Foundation, and in collaboration with Dr. Shawna Willey, his team is using nipple aspirate fluid and ductal lavage as minimally invasive procedures that permit the collection of breast cells from patients for early detection and diagnosis of breast cancer. This approach will benefit particularly women at high-risk for breast cancer who require frequent and closer monitoring.

Dr. Shields, in collaboration with Drs. Blancato, Byrne, Loffredo, Freedman, Seillier-Moiseiwitsc, Mamambe, Dickson, Furth, Sidawy and Johnson, has established a extensive set of studies examining 180 breast tissues from women undergoing reduction mammoplasty. This was funded using Lombardi institutional and then DOD Center of Excellence monies. These are women with no history of breast cancer, although might have a slightly higher risk of breast cancer because of there large breasts. Studies are ongoing that are examining epigenetic, protein expression and breast cell and lobular differentiation in relation to known breast cancer risk factors, blood hormone levels and mammographic breast density. So far, they have identified that 9-36% of these health women have evidence of promoter hypermethylation of p16, ER-alpha and BRCA1, and having BRCA1 hypermethylated increases the risk for ER hypermethylation by 8-fold (manuscript submitted). There also was an association with family history of breast and other cancers, which differed by race.

Dr. Shields and his research team have validated methods for the detection of genetic polymorphisms and mutations in paraffin-embedded breast and lung tumors, specifically reporting on the detection of p53 mutations in paraffin-embedded breast and lung tumors dating back to 1958 (Prochazka et al, 2005). With Dr. Singh, they demonstrated that genotyping of embedded normal tissue adjacent to tumor does not result in genotype misclassification due to field effects (Xie et al, 2005). The p53 detection methodology also has been applied to liver tumor samples collected by Dr. Loffredo in Egypt, and they showed that similar p53 mutations are detected as those found in high aflatoxin regions (El-Kafrawy et al, 2005).

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Population studies of breast cancer
Investigators: Byrne, Shields, Freedman, Loffredo, Gail, Haddad, Martin, Marian, Kallakury, Singh, Jorgensen, Kallakury, Hall (Sweden), Granath (Sweden), Adams-Campbell

The study of breast cancer promotes substantial collaborations with the BC, GRC, and CC programs. The CBE Program is the only program with epidemiologists, and their methods for studying breast cancer in populations differ from and augment clinical and basic science invest investigations related to the genetic predictors of breast cancer in populations, and phenotypic predictors of breast cancer such as mammographic breast density and markers of DNA repair.

Dr. Byrne is known for her studies on mammographic breast density and breast cancer risk. While continuing work that began with her studies at Harvard University (Tamimiet al., 2005), she now collaborates with Drs. Shields, Freedman and Loffredo to conduct a cross-sectional study of 1,600 White and African American women funded by the DOD COE. The hypothesis is that there are genetic determinants that increase breast density associated with alcohol drinking. She also is funded by the Susan G. Komen Foundation to study IGF levels in this population. Dr. Byrne has co-authored a publication that resulted from her long-term work with Dr. Mitchell Gail to incorporate measures of mammographic breast density into a statistical model to project the absolute invasive breast cancer risk in white women (Chen et al., 2006). Dr. Byrne also has an ongoing collaboration with researchers in Quebec for a study of dietary correlates with breast density; higher intakes of vitamin D and calcium from food and supplements were related to lower levels of breast density among premenopausal women (Diorio et al., 2006). Dr. Byrne is collaborating with Drs. Haddad and Martin  on new pilot projects supported by Lombardi developmental funds to investigate genetic polymorphisms in the IGF and nitrate pathways as risk markers of breast cancer.  

Dr. Shields has been using to breast cancer case-control studies performed by Dr. Jo Freudenheim (SUNY, Buffalo) in upstate New York, which has resulted in about 20 publications. Also at Lombardi, current collaborators include Drs. Marian and Kallakury. They recently reported that catalase genotypes affect postmenopausal breast cancer in association with hormone replacement therapy (Quick, et al, 2008) and that hypermethylation of tumor suppressor genes vary with clinicopathological features (Tao, 2008), An extensive characterization of more than 800 breast cancer cases is now completed, including the completion of assays for p53 mutations, hypermethylation of tumor suppressor genes, immunohistochemistry (ER, PR, Ki-67, Her2Neu), mitochondrial DNA mutations, and comparative genomic hybridization. They have found that for postmenopausal women, hypermethylation of E-cadherin occurred more frequently in progesterone receptor negative tumors, hypermethylation of p16 occurred more frequently in estrogen receptor (ER) negative cases and hypermethylation of RAR-beta(2) gene was inversely associated with histological and nuclear grade of breast cancer (Tao, manuscript submitted). They also replicated the FGFR2 SNP breast cancer association found in prior GWAS studies, and identified modification of the FGFR2 association by smoking status and adiposity (Marian, manuscript submitted). Among premenopausal cases, p53 status was associated with ER-/PR- tumors and among postmenopausal women, p53 was associated with higher BMI, higher grade tumors, poor differentiation ), ER-/PR- status, and tumors bigger that 2 cm (Marian, manuscript submitted). When stratifying by mutation type, only p53 transitions mutations were positively associated in postmenopausal women with grade, KI67 and ER/PR status, and transversions were associated with BMI. Postmenopausal cases with p53 mutations also had a 2.4 fold increased risk of breast cancer mortality after adjusting for other prognostic factors (Marian, manuscript submitted).

In an RO1-funded study of secondary lung cancer risk in breast cancer survivors, Drs. Shields, Singh, Jorgensen  and Kallakury, and collaborators in Sweden (Per Hall and Frederik Granath), have identified more than 600 cases, and retrieved tumor blocks of both cases and controls, and for 600 matched breast cancer cases. They have reported that radiotherapy for breast cancer significantly increases the risk of lung carcinoma more than 10 years after exposure in women who also smoked at time of breast cancer (Prochazka et al., 2005). They are now studying p53 mutations and hypermethylation.The feasibility of this study was reported (Tennis, 2006).

Dr. Shields, with Dr. Adams-Campbell, assessed 61 African American breast cancer cases and 81 controls from Howard University and showed that the mutagen sensitivity assay increased breast cancer risk by 4.5-fold, and that co-culturing with caffeine that decreases G2/M arrest and time for DNA repair provides different response patterns in cases and controls (Natarjan, 2006).

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Population studies of liver cancer
Investigators: Loffredo, Shields, Goldman, Ressom

Several CBE members now collaborate on studies of hepatocellular carcinoma (HCC), which investigate the interrelated roles of viral and parasitic infections, environmental carcinogens, and genetic susceptibility.

Dr. Christopher Loffredohas developed a collaborative network for conducting epidemiology studies in Egypt, with support from three separate R01s. Initially, Dr. Loffredo developed a case-control study of HCC in 1999, which was subsequently renewed competitively (2R01CA85888-09). The aims are to assess the association of HCC with viral risk factors (hepatitis C and B viruses, HCV and HBV), environmental factors (pesticides and tobacco smoking), and genetic risk factors (genetic polymorphisms in enzymes that mediate the toxicity of environmental exposures). Over 5,000 subjects have been enrolled in these studies. Findings on pesticides, tumor markers and the genetic diversity of HCV have been published (Abdel-Hamid et al, 2007; Nada et al, 2005; Ezzat et al, 2005). One example of this work (Ezzat et al. 2005) asserts that HCC risk from HCV is greater for men than women overall, and with rural men having an elevated risk from occupational exposure to organophosphate pesticides. A separate arm of the study is to investigate the association of HCV with B-cell non-Hodgkin's lymphoma (NHL), a less well known malignant outcome of chronic HCV infection (Cowgill et al, 2004). A secondary aim is to identify sequence mutations in the p53 gene within tumor tissues, in collaboration with Dr. Shields (El-Kafrawy et al., 2005). Based on this body of work, Dr. Loffredo was invited to become a founding member and the head of the Epidemiology Committee of the International Liver Cancer Consortium, which aims to foster genome-wide association studies and other data pooling projects.

Dr. Goldman's R01 grant on liver cancer proteomics (see Section 6.2.1 above) and newly awarded R01 on glycan signatures in sera uses specimens and clinical and epidemiological data from Dr. Loffredo's study, and is an example of both successful mentoring and of intra-programmatic collaboration with Drs. Loffredo and Ressom.

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Population studies of tobacco use and related cancers
Investigators: Loffredo, Shields, Goldman, Zheng, Rice,

Dr. Loffredo was the PI of a recently completed NIH Fogarty International Center 5-year R01 grant to establish and implement the Egyptian Smoking Prevention Research Institute (ESPRI). The overall goal of ESPRI is to conduct tobacco prevention and research to assist Egypt in building the necessary infrastructure and research capability to manage the public health threat of tobacco. Dr. Loffredo, together with Drs. Shields and Goldman of the CBE Program, and I. Jillson of the Georgetown University School of Nursing, is conducting intervention studies among women and youths, and molecular epidemiology studies of biomarkers of tobacco harm and of genetic susceptibility to nicotine addiction. The team has published twelve peer-reviewed articles to date (e.g. Labib et al. 2007; Radwan et al. 2007) and was commissioned by the World Health Organization to write a monograph on waterpipe tobacco smoking which was published in 2006 (World Health Organization: 2006).

Dr. Loffredo also is conducting a bladder cancer case-control study (NCI R01CA115614). This 5-year project, performed in collaboration with Drs. Shields, Zheng, and Rice, will study gender differences in risk factors for bladder cancer, including infectious and parasitic diseases, environmental factors, and genetic background. When completed, the study will be among the largest epidemiologic studies ever conducted in bladder cancer, with 2,000 cases and 6,000 age- and gender-matched population-based controls. This study is part of the International Bladder Cancer Consortium, which has recently begun genome-wide association studies.

Dr. Loffredo, together with Drs. Shields and Zheng and Dr. Curt Harris at the NCI, founded the Maryland Lung Cancer Study in 1998 to study genetic risk factors for lung cancer; the project is ongoing. This involved establishment of a collaborative network of six hospitals in Baltimore, Maryland, funded by the intramural program of the NCI. Dr. Loffredo is the study's epidemiologist and Dr. Zheng conducts biomarker assays. It is a case-control study of subjects with pathologically-confirmed non–small cell lung cancer in comparison to matched cancer-free hospital controls and population-based controls. Individual sensitivity to bleomycin-induced chromosome breaks was found to be predictive of lung cancer risk (Zheng et al, 2003). These data also indicated that deficiencies in the function of G2/M cell cycle checkpoint are associated with an increased risk of lung cancer among African Americans (Zheng et al, 2005). In another project based on the data and specimens of this study population, Pine et al (2007) reported that lung cancer survival is associated with functional polymorphisms in MBL2, an innate-immunity gene. In addition, the group recently published an analysis of the occupational history data of these subjects (Amr et al, 2008), showing that African American women had the highest risks for lung cancer associated with service occupations such as cleaning and maintenance work.

Funding for a substantial infrastructure has recently been awarded via a competitive N01 contract mechanism from the NCI to study new tobacco products, as mentioned above. The N01 contract (PI: Shields) funds research related to the behavior of tobacco use, toxicology, and biomarkers in humans and risk assessment, as it relates to harm reduction. This contract is funding a number of studies to develop a large biorepository of samples from well-characterized smokers, former smokers and ex-smokers, as well as people enrolled in smoking cessation studies and clinical trials of persons testing new tobacco products. A large clinical trial is currently being planned for assessing smokers dual users of smokeless tobacco and complete switchers to smokeless tobacco.

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Population studies of other cancer types
Investigators: Genkinger, Smith-Warner (Pooling Project of Prospective Studies of Diet and Cancer Investigators), Chung, Davidson, Kallakury

Many of the studies described herein are epidemiological pilot projects intended to further larger, collaborative studies.

Dr. Jeanine Genkinger, a recently recruited epidemiologist who trained at both Johns Hopkins and Harvard Universities, is conducting a pilot study of colorectal cancer at GUMC, funded by Lombardi developmental funds. The goals are to recruit 100 cases prior to treatment, and measure factors previously associated with survival (especially aspects of diet and obesity) during the first year post-surgery, and to measure changes in these factors over that time period.

In collaboration with Dr. Smith-Warner of the Pooling Project of Prospective Studies of Diet and Cancer Investigators, Dr. Genkinger has completed and published several analyses (Genkinger et al. 2006, 2007) where hypotheses on cancer risk factors and prevention were tested across cohort studies with thousands of pooled subjects. Separately, alcohol drinking has been found to be associated with pancreatic cancer (Genkinger, manuscript submitted).

Dr. Chung is also conducting research on the mechanisms of green tea in the prevention of human cancer, collaborating with Dr. Bruce Davidson  and Dr. Kallakury to conduct an intervention trial in smokers using oral cells. This project is supported by an NCI R01 grant entitled "Prevention of Oral Cancer in Smokers by Tea: A Mechanism Study".