5735 results for "canc*"

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• Neoadjuvant Trastuzumab Response in Breast Cancer

  HER2 (ERBB2) gene amplification and overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents such as trastuzumab are effective treatments, therapeutic resistance remains a concern in HER2-positive breast cancer with 40-50% of patients having residual disease after neoadjuvant treatment with chemotherapy and trastuzumab. To investigate features that may make it possible to predict at diagnosis which cancers will be responsive to trastuzumab and chemotherapy, 48 tumor/normal DNA pairs extracted from pretreatment tumor biopsies and blood of HER2-positive breast cancer cases treated with neoadjuvant chemotherapy and trastuzumab were sequenced. Whole genome and exome sequence from tumor (average depth 49x and 71x) and normal (average depth 33x and 69x) DNA are included here as well as RNAseq data for 42 of the tumors. The study cohort was equally divided between patients who experienced pathological complete response and those with residual disease. Samples were obtained from the American College of Surgeons Oncology Group Z1041 trial (NCT00513292) and a local single-institution study (NCT00353483).

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• Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) - OncoArray Genotypes

  The data come from 40 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). CIMBA recruits individuals with pathogenic mutations in BRCA1 or BRCA2. The majority of carriers were recruited through cancer genetics clinics offering genetic testing, and were enrolled into national or regional studies. The remainder were identified by population-based sampling of cases, or community recruitment. Eligibility to participate is restricted to carriers of pathogenic BRCA1/2 mutations who were 18 years or older at recruitment. Information collected included amongst other variables: age at recruitment; ages at breast and ovarian cancer diagnosis; and estrogen receptor (ER) status. Samples were genotyped using the Illumina OncoArray beadchip 500K SNP custom array. Details of the genotyping process and sample selection are included in Phelan et al, Identification of twelve new susceptibility loci for different histotypes of epithelial ovarian cancer, Nat Genet. 2017 May;49(5):680-691 (PMID:28346442), and Milne et al, Identification of ten variants associated with risk of estrogen receptor negative breast cancer, Nat Genet (in press).

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• Genome-Wide Association Study of Sporadic and Familial Testicular Germ Cell Tumors

  Case-Control Study:Testicular germ cell cancer has been increasing among men during most of the 20th century. Despite this increase, the etiology of testicular cancer is poorly understood. To better understand the molecular epidemiology of testicular cancer, the National Cancer Institute and the Department of Defense are conducting a case-control study of testicular cancer among military servicemen. The project includes obtaining biosamples and questionnaire data from all participants. Pre-diagnostic serum samples are available from the approximately 1,000 cases and 1,000 controls enrolled in the study. Multiple-Case Family Study:In a parallel project, we are also studying families in which 2 or more testicular cancers have occurred. Among those men diagnosed with testicular cancer, about 1-3 percent report a family history of the disease (FTGCT). Brothers of affected individuals are 8 to 10 times more likely to develop testicular cancer, and men whose fathers had testicular cancer are four times more likely to develop testicular cancer, when compared with the relatives of men who have never had testicular cancer. Large-scale genetic linkage studies have failed to identify one or more rare, highly-penetrant testicular susceptibility genes. Rather, it appears that these familial clusters are due to the combined effects of multiple more common genes with low penetrance (so-called "polygenic inheritance"). Our cohort of FTGCT families was assembled to characterize this syndrome's clinical phenotype, and to discover the full range of cancer susceptibility loci that influence TGCT pathogenesis.

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• National Cancer Institute (NCI) Biospecimen Pre-analytical Variables (BPV) Analysis

  The Biospecimen Pre-analytical Variables (BPV) Program is a National Cancer Institute-sponsored study to systematically assess the effects of pre-analytical factors on the molecular profile of biospecimens. A robust biospecimen collection infrastructure was established to prospectively collect biospecimens using rigorous standard operating procedures to control for most variables while introducing experimental conditions to study specific biospecimen handling issues, including the cold ischemic time (delay to formalin fixation), time in formalin, freezing methods, and storage temperatures and durations. RNA and DNA from biospecimens collected under these conditions was analyzed on multiple molecular platforms. The potential effects of these pre-analytical conditions on protein integrity and detection of metabolites were also examined. Data from this study will be used to develop evidence-based biospecimen standard operating procedures and best practices for fit-for-purpose collection, processing, and storage of biospecimens. The BPV Cohort is utilized in the following dbGaP substudies. To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following sub-studies below or in the "Substudies" box located on the right hand side of this top-level study page phs001304 BPV Cohort. The substudy links will be active once they are released by dbGaP. Preanalytical Impacts on Global Metabolite Profiling - plasma (MassSpec by Metabolon) This study was to evaluate the impact of the storage temperature (s) (-80°C and LN2 vapor) and the length of storage on human plasma quality using LC-MS/MS (liquid-chromatography-mass spectrometry/mass spectrometry) based global metabolite profiling. The study includes 240 plasma samples collected from 40 donors. Investigate the effect of the delay to fixation on the proteome and phosphoproteome -FFPE (MassSpec by Caprion). The study is to do proteome and phosphoproteome analysis on Delay to fixation was carried out using FFPE tumor samples from colon and ovarian cancer patients comparing 2, 3, and 12hr delay to fixation to the 1hr time point. The study includes 100 samples 20 donors. Investigate the effect of storage conditions of tumor specimens on the proteome and phosphoproteome profiling- Frozen tissue and plasma (MassSpec by Caprion). The study was to evaluate the effects of storage conditions on tumor specimens. Plasma samples from 40 cancer patients stored at two different temperatures (-80°C and LN2) for a given period (0-2, 6-8, and 12-14 months) were evaluated. Frozen kidney tumor samples from 20 patients were compared for effects of different snap frozen (dry ice vs. LN2) and storage temperatures (-80°C and LN2). The study includes 100 tissue and 240 plasma samples from 60 donors. Preanalytical Impacts on Genomic Sequencing by Next Generation Sequencing (NGS) technology (mRNA/miRNA and WES by Expression Analysis). The goal of the study is to determine the effects of cold ischemic delay-to-fixation (4 time points) and formalin preservation (FFPE) on the nature and quality of genomic profiles using the matched freshly frozen sample as the gold standard, which including WES, RNAseq. The study includes 395 samples from 37 donors. Preanalytical Impacts on Copy Number Variation (CNV) Detection by aCGH technology (aCGH by Georgetown University). This study was to use aCGH to evaluate the effect of variation in cold ischemia time and time in formalin fixation on CNV in DNA extracted from kidney cancer specimens. The study includes 235 samples from 40 donors. Evaluation of frozen conditions on mRNA profiling by TaqMan assay (mRNA expression by Georgetown University). This study was to utilize gene expression profiling, using custom TaqMan arrays, to compare the molecular profiles of RNA from frozen tumor samples collected using two freezing methods (dry ice or LN2), two storage temperatures (-80°C or LN2 vapor), as well as Optimal Cutting Temperature (OCT) compound and non-OCT embedded. The study includes 100 samples from 20 donors. mRNA signature for stratification by cold ischemia time (mRNA expression by IBBL). The study was to determine the effects of cold ischemic time (delay-to-fixation) and formalin preservation (FFPE) on mRNA detection by Taqman assay using tumor tissue specimens from kidney, colon and ovarian cancer patients. There are160 samples from 40 donors. The Biospecimen PV cohort is utilized in the following dbGaP individual studies. To view molecular data, and derived variables collected in these individual studies, please click on the following individual studies below or in the "Sub-studies" box located on the right hand side of this top-level study page phs001304 Biospecimen PV cohort. phs001634 CIT mRNA phs001635 CNV aCGH phs001636 Fixation Delay phs001637 Global Metabolite Profiling phs001638 mRNA TaqMan phs001639 NGS phs001640 Tumor Storage

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• Inherited Genetic Variation and Predisposition to Testicular Germ Cell Tumor: UPenn Local TGCT Study

  Testicular germ cell tumors (TGCT) are the most common cancer in men ages 20-40. The incidence of TGCT has more than doubled over the past forty years, without clear etiology. Both genetic effects and environmental exposures, specifically during the pre-natal period, are likely to play an important role in determining TGCT susceptibility. TGCT is known to develop from primordial germ cells (PGCs). We hypothesize that variation in genes that impact upon the differentiation and maturation of PGCs will be important determinants of TGCT susceptibility and based on this hypothesis have selected three important pathways for study, i) male germ cell development, ii) androgen and estrogen biosynthesis and metabolism, and iii) IGF signaling. The proteins involved in early male germ cell development, normally only expressed in PGCs, are markers of and are overexpressed in TGCT. Markers of increased exposure to estrogen (or relatively decreased exposure to androgen) in utero and exogenous estrogen exposures, such as endocrine disruptors, have been associated with TGCT case status in multiple studies. IGF signaling is necessary for testis differentiation and maturation in mice and interacts synergistically with the estrogen signaling pathway. Additionally, we are interested in examining genetic factors predisposing to TGCT in an unbiased fashion, and thus will conduct a Genome Wide Association Study. As well disease susceptiblity, genetics are likely to play a role in disease progression, disease outcomes and response to treatement. We will also assess association of inherited genetics with these outcomes. We will analyze the contribution of genetic variants in these pathways to TGCT risk using a population-based case-control study in the Philadelphia metropolitian area. Our goal is the collection of 550 TGCT cases and 1100 age, race and cell phone use matched controls without a history of TGCT, which will yield 500 and 1000 white cases and controls, respectively, available for final analyses. All cases will be enumerated through the New Jersey and Pennsylvania state cancer registries. We will use a two-tiered approach for case recruitment: hospital clinic-based followed by registry-based. Hospital based cases will be identified within the Univeristy of Pennsylvania Health System and the University of Pennsylvania Cancer Network. All cases identified through this mechanism will be recruited irregardless of diagnosis date. The remaining cases will be identified through the New Jersey and Pennsylvania cancer registries and contacted following their protocols. Controls will be identified through random digit dialing and address based sampling. Both cases and controls will complete a questionnaire addressing known, presumed, and hypothesized risk factors for TGCT and provide a biospecimen. Pathological slides will be reviewed to cases to confirm diagnostic sub-type of TGCT. Haplotypes and functional SNPs will be typed in the genes of interest, as well as throughout the genome. Analyses will be conducted for specific variants, common haplotypes, alone and in conjunction with each other and exposure data after appropriate adjustment for potential confounders. The findings from this study will greatly contribute to our understanding of determinants of TGCT susceptibility.

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• GECCO: Detecting Common and Rare Genetic Loci and GxE Interactions in Colorectal Cancer

  COLON, Colorectal Cancer: Longitudinal Observational study on Nutritional and lifestyle factors that influence colorectal tumor recurrence, survival and quality of life: The COLON study is a multi-center prospective cohort study to assess the role of diet and other lifestyle factors in cancer recurrence and survival among incident colorectal cancer patients in the Netherlands. DACHS, Darmkrebs: Chancen der Verhütung durch Screening:This German study was initiated as a large population-based case-control study in 2003 in the Rhine-Neckar-Odenwald region (southwest region of Germany) to assess the potential of endoscopic screening for reduction of colorectal cancer risk and to investigate etiologic determinants of disease, particularly lifestyle/environmental factors and genetic factors. During an in-person interview, data were collected on demographics, medical history, family history of CRC, and various life-style factors, as were blood and mouthwash samples. EPIC, European Prospective Investigation into Cancer: EPIC is an on-going multicenter prospective cohort study designed to investigate the associations between diet, lifestyle, genetic and environmental factors and various types of cancer. HPFS, Health Professionals Follow-up Study: HPFS is a parallel prospective study to the NHS. The HPFS cohort comprised 51,529 men aged 40-75 who, in 1986, responded to a mailed questionnaire. Participants provided information on health related exposures, including current and past smoking history, age, weight, height, diet, physical activity, aspirin use, and family history of colorectal cancer. Colorectal cancer and other outcomes were reported by participants or next-of-kin and were followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical record review. Information was abstracted on histology and primary location. Follow-up evaluation has been excellent, with 94% of the men responding to date. NHS, Nurses' Health Study: The NHS cohort began in 1976 when 121,700 married female registered nurses age 30-55 years returned the initial questionnaire that ascertained a variety of important health-related exposures [PMID:248266]. Since 1976, follow-up questionnaires have been mailed every 2 years. Colorectal cancer and other outcomes were reported by participants or next-of-kin and followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical-record review. Information was abstracted on histology and primary location. The rate of follow-up evaluation has been high: as a proportion of the total possible follow-up time, follow-up evaluation has been more than 92%. NQplus, Nutrition Questionnaires plus: NQplus is a longitudinal observational study on diet and health in the general Dutch population.

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• Glioma International Case Control Study (GICC)

  The main goals of the GICC Study were: 1) to identify novel genetic risk variants for glioma, as well as validate variants implicated by previous genome-wide association studies of glioma; and 2) to explore biologically relevant gene-gene and gene-environment interactions in glioma susceptibility. The GICC Study includes participants from the following centers: Brigham and Women's Hospital (Boston, Massachusetts), Case Western Reserve University (Cleveland, Ohio), Columbia University (New York, New York), the Danish Cancer Society Research Centre (Copenhagen, Denmark), Duke University (Durham, North Carolina), the University of Texas MD Anderson Cancer Center (Houston, Texas), Memorial Sloan Kettering Cancer Center (New York, New York), the Mayo Clinic (Rochester, Minnesota), NorthShore HealthSystem (Chicago, Illinois), Umea University (Umea, Sweden), the University of California, San Francisco (San Francisco, California), the University of Southern California (Los Angeles, California), and the Institute of Cancer Research (London, United Kingdom).

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• Childhood Cancer Survivor Study (CCSS)

  Background and Rationale for the Childhood Cancer Survivor Study (CCSS) Over the last several decades, advances in treatments for childhood and adolescent cancer have substantially improved survival following diagnosis. These improvements gave rise to the responsibility for investigating long-term treatment-associated morbidity and mortality. Early efforts to describe late effects were largely conducted through single-institution and limited consortia studies. However, by the mid-1980s, it became increasingly clear that these approaches had inherent limitations, including small sample size, convenience sampling, incompletely characterized populations, and limited length of follow-up. To overcome these limitations, the CCSS was proposed and funded by the National Cancer Institute (NCI) as a U01 grant in 1994. Subsequently, the strengths of the CCSS, including an efficient and extensive infrastructure, plus expanding database and biorepository, were recognized and appreciated. Thus, in consultation with the NCI, the CCSS was converted to a U24 (resource grant) funding mechanism to serve the scientific community in 2000. The overarching goal of the CCSS resource is to increase the conduct of innovative and high impact research related to pediatric cancer survivorship. CCSS has been used extensively by researchers from a wide range of disciplines to address a broad spectrum of topics. Strengths of the resource include its large size, comprehensive annotation of treatment exposures, ongoing longitudinal follow-up with characterization of a wide array of participant characteristics and outcomes, and an established biorepository. Design of the Childhood Cancer Survivor Study The Childhood Cancer Survivor Study (CCSS) is a multi-institutional, multi-disciplinary collaborative research resource comprised of a retrospective hospital-based cohort of survivors of childhood cancer and a comparison sibling cohort. Eligible survivors from 31 participating institutions were diagnosed between 1970 and 1999, prior to age 21 years, with selected common pediatric cancers (leukemia, central nervous system tumors, Hodgkin lymphoma, non-Hodgkin lymphoma, kidney tumors, neuroblastoma, soft tissue sarcoma, or bone tumors). All patients who survived five years from the date of diagnosis were eligible, regardless of disease or treatment status. The baseline questionnaire was completed by 24,368 survivors and 5,039 siblings recruited to serve as a comparison group. To date, participants have completed three general follow-up surveys, as well as a number of specialized surveys on specific topics (e.g. health care, insurance, screening practices, men's and women's health issues, adolescent health, sleep and fatigue). In addition, biological samples (buccal cells, saliva and/or blood) have been collected for over 11,000 participants. Full descriptions of the design and characteristics of the CCSS have been previously published (Robison et al; Leisenring et al.), and available data and samples are described at https://ccss.stjude.org/develop-a-study/gwas-data-resource.html. Treatment Data in the Childhood Cancer Survivor Study A key feature of CCSS is the availability of detailed treatment data, which were collected by abstraction of medical records for each individual member of the cohort. Detailed abstraction included dates of therapy, protocol information, and specific details regarding surgery, chemotherapy and radiation. Quantitative dose details were collected for 22 specific chemotherapeutic agents, including alkylating agents, anthracyclines, platinum compounds and epipodophyllotoxins. In addition to individual agent doses, algorithms have been created to calculate cumulative doses of all drugs in a specific class, such as anthracyclines (doxorubicin, daunomycin and idarubicin) or platinum agents (cisplatinum and carboplatinum). Data abstracted for surgeries included dates and both the names and corresponding International Classification of Diseases (9th revision) code. For radiation treatment data, all relevant records were sent to the Radiation Physics Center at M.D. Anderson Cancer Center for detailed abstraction and dosimetry. Initial body region dosimetry was performed for all participants, followed by more detailed dosimetry as needed for specific studies. Genomics Data in the Childhood Cancer Survivor StudyThe NCI's Division of Cancer Epidemiology and Genetics and CCSS investigators collaborated to conduct genomics studies (SNP array genotyping and whole exome sequencing) using samples from the CCSS Biorepository. Studies included all cohort participants with available DNA regardless of sex or ancestry when the genomics studies were initiated. Phenotype Data in the Childhood Cancer Survivor Study Vital status and cause of death for both participants and non-participants is determined via linkage with the National Death Index (NDI). Identification of subsequent neoplasms is based on self-report, followed by validation using medical records, or via NDI. A wide array of additional health outcomes have been ascertained via a comprehensive set of questions on the CCSS questionnaires, covering potential adverse events across a range of organ systems (hearing/vision/speech, urinary, hormonal, heart and circulatory, respiratory, digestive, brain and nervous systems). In addition to health outcomes, longitudinal data have been collected on demographics, health behaviors, family history, screening practices, insurance status, and a range of psychosocial and neurocognitive factors. A full listing of available variables and copies of the CCSS questionnaires are available at http://ccss.stjude.org. Research Areas in the Childhood Cancer Survivor Study Extensive use by the research community has resulted in over 265 published manuscripts on a wide range of topics, including associations between treatment factors and mortality, subsequent neoplasms, chronic health conditions, cardiac events, neurocognitive sequelae, psychosocial factors, fertility, and health status. Additional topics have included health behaviors, screening practices, health care access and utilization, statistical and exposure assessment methodology, and development of risk prediction models. A full listing of published manuscripts using CCSS data is available on the CCSS website at https://ccss.stjude.org/published-research/publications.html. The Childhood Cancer Survivor Study as a Resource for Investigators The CCSS is an NCI-funded resource (U24 CA55727) to promote and facilitate research among long-term survivors of cancer diagnosed during childhood and adolescence. Interested investigators are encouraged to develop research ideas and propose projects within CCSS, whether or not they are from a participating CCSS institution. The CCSS is now accepting proposals to collaborate with CCSS and NCI investigators in the use of genomics data and corresponding outcomes-related data to address innovative research questions relating to potential genetic contributions to risk for treatment-related outcomes. Any researcher, or group of researchers, qualified to conduct genetic research can submit a proposal. There are no restrictions relative to country, institution, or prior involvement in CCSS. A full description of the process for developing a proposal for genetic research in CCSS can be found at https://ccss.stjude.org/develop-a-study/gwas-data-resource.html, along with listings of approved proposals.

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• AACR Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE)

  AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international pancancer registry of real-world data assembled through data sharing between 19 leading international cancer centers with the goal of improving clinical decision-making. The registry leverages ongoing clinical sequencing efforts (CLIA/ISO-certified) at participating cancer centers by pooling their data to create a novel, open-access registry to serve as an evidence base for the entire cancer community. Genomic and baseline clinical data from more than 70,000 tumors is accessible through the efforts of our strategic and technical partners, Sage Bionetworks and cBioPortal. The consortium and its activities are driven by openness, transparency, and inclusion to ensure that the project output remains accessible to the global cancer research community and ultimately benefits patients.

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• Identification of 22 Novel Loci Associated with Susceptibility to Testicular Germ Cell Tumors

  Testicular germ cell tumors (TGCT) are the most common cancers in young men of European ancestry aged 20 to 39 years. The Testicular Cancer Consortium (TECAC) has brought together the largest genome-wise association study (GWAS) study of TGCT to date. We conducted a GWAS of 5,602 cases and 5,006 controls aggregated from 12 locations in the US and Europe. Logistic regression models adjusted for study center and genomic ancestry. Genotypes were imputed against the Human Haplotype Reference Consortium. Meta-analysis was performed to combine GWAS results with summary statistics from five previously published TGCT studies, UK Biobank, deCODE Genetics, and an independent set of cases and controls, for a total of 10,156 cases and 179,683 controls. 22 novel and 45 previously reported loci associated with TGCT surpassed genome-wide significance (p < 5e-08).

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