The University of North Carolina Cancer Survivorship Cohort: A Resource for Collaborative Survivorship Research.

Background: Rapid growth in the number of US cancer survivors drives the need for ongoing research efforts to improve outcomes and experiences after cancer. In this study, we describe the University of North Carolina (UNC) Cancer Survivorship Cohort, a medical center-based cohort of adults with cancer that integrates medical record-abstracted cancer information, patient-reported outcomes, and biological specimens.

Methods: Participants ages 18+ were recruited from UNC oncology clinics between April 2010 and August 2016.

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included.

Race, the Vaginal Microbiome, and Spontaneous Preterm Birth.

Previous studies have investigated the associations between the vaginal microbiome and preterm birth, with the aim of determining whether differences in community patterns meaningfully alter risk and could therefore be the target of intervention. We report on vaginal microbial analysis of a nested case-control subset of the Pregnancy, Infection, and Nutrition (PIN) Study, including 464 White women (375 term birth and 89 spontaneous preterm birth, sPTB) and 360 Black women (276 term birth and 84 sPTB). We found that the microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners, and lower abundance of Lactobacillus crispatus.

Is prenatal diet associated with the composition of the vaginal microbiome?

Background: The vaginal microbiome has been associated with adverse pregnancy outcomes, but information on the impact of diet on microbiome composition is largely unexamined.

Objective: To estimate the association between prenatal diet and vaginal microbiota composition overall and by race.

Methods: We leveraged a racially diverse prenatal cohort of North Carolina women enrolled between 1995 and 2001 to conduct this analysis using cross-sectional data.

Cohort Profile: ZOE 2.0-A Community-Based Genetic Epidemiologic Study of Early Childhood Oral Health.

Early childhood caries (ECC) is an aggressive form of dental caries occurring in the first five years of life. Despite its prevalence and consequences, little progress has been made in its prevention and even less is known about individuals' susceptibility or genomic risk factors. The genome-wide association study (GWAS) of ECC ("ZOE 2.

Germline 16p11.2 Microdeletion Predisposes to Neuroblastoma.

Neuroblastoma is a cancer of the developing sympathetic nervous system. It is diagnosed in 600-700 children per year in the United States and accounts for 12% of pediatric cancer deaths. Despite recent advances in our understanding of this malignancy's complex genetic architecture, the contribution of rare germline variants remains undefined.

Neuroblastoma in relation to joint effects of vitamin A and maternal and offspring variants in vitamin A-related genes: A report of the Children's Oncology Group.

Background: There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake.

The Supragingival Biofilm in Early Childhood Caries: Clinical and Laboratory Protocols and Bioinformatics Pipelines Supporting Metagenomics, Metatranscriptomics, and Metabolomics Studies of the Oral Microbiome.

Early childhood caries (ECC) is a biofilm-mediated disease. Social, environmental, and behavioral determinants as well as innate susceptibility are major influences on its incidence; however, from a pathogenetic standpoint, the disease is defined and driven by oral dysbiosis. In other words, the disease occurs when the natural equilibrium between the host and its oral microbiome shifts toward states that promote demineralization at the biofilm-tooth surface interface.

Protocols, Methods, and Tools for Genome-Wide Association Studies (GWAS) of Dental Traits.

Oral health and disease are known to be influenced by complex interactions between environmental (e.g., social and behavioral) factors and innate susceptibility.

Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.

Background: Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.

Exploring the genomic basis of early childhood caries: a pilot study.

Objective: A genetic component in early childhood caries (ECC) is theorized, but no genome-wide investigations of ECC have been conducted. This pilot study is part of a long-term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC-associated genetic loci.

Methods: The study's community-based sample comprised 212 children (mean age=39 months; range = 30-52 months; males = 55%; Hispanic/Latino = 35%, African-American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%).

A family-based study of gene variants and maternal folate and choline in neuroblastoma: a report from the Children's Oncology Group.

Purpose: Neuroblastoma is a childhood cancer of the sympathetic nervous system with embryonic origins. Previous epidemiologic studies suggest maternal vitamin supplementation during pregnancy reduces the risk of neuroblastoma. We hypothesized offspring and maternal genetic variants in folate-related and choline-related genes are associated with neuroblastoma and modify the effects of maternal intake of folate, choline, and folic acid.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts.

Collecting Biospecimens From an Internet-Based Prospective Cohort Study of Inflammatory Bowel Disease (CCFA Partners): A Feasibility Study.

Background: The Internet has successfully been used for patient-oriented survey research. Internet-based translational research may also be possible.

Objective: Our aim was to study the feasibility of collecting biospecimens from CCFA Partners, an Internet-based inflammatory bowel disease (IBD) cohort.

Design of a multi-center immunophenotyping analysis of peripheral blood, sputum and bronchoalveolar lavage fluid in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Background: Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument.

Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study.

Background: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100).

Methods: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects.

Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality.

Background: Environmental, lifestyle, and occupational exposures on semen quality have been investigated in epidemiological studies with inconsistent results. Genetic factors involved in toxicant activation and detoxification have been examined in relation to the risk of outcomes such as cancer, cardiovascular, and neurologic disorders. However, the effect of common genetic variants in the metabolism of toxicants on semen quality parameters has rarely been evaluated.

Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.

Background: The Pentose Phosphate Pathway (PPP) is involved in the body's protection against oxidative stress and resistance/susceptibility to apoptosis and thus has been implicated in tumor development and progression. Here we present data examining the association of genetic variation in one of the key enzymes of the PPP, Transaldolase 1 (TALDO1) with squamous cell carcinoma of the head and neck (SCCHN).

Methods: We performed sequencing analysis to identify common genetic variations in TALDO1 and then investigated their association with SCCHN using samples from a population-based case/control study with both European American (EA) and African American (AA) former and current smokers.

Microsatellite analysis in FVB/N mice.

The purpose of the study reported here was to identify, by size, a set of microsatellite markers for use in diagnostic genetic monitoring of FVB/N mouse colonies. A large panel of microsatellite markers were chosen on the basis oftheir high degree of allelic variability. These markers were then tested for their ability to amplify well under a standard set of polymerase chain reaction analysis conditions and to present an easily identifiable band on an agarose gel.

Preparation of monoclonal antibodies reactive to the endogenous small molecule, anandamide.

The development of an easy and inexpensive immunoassay to measure the limited quantities of endogenous cannabinoids found in the body would be beneficial for both cannabinoid researchers and clinicians. This report describes the hapten design and carrier molecule strategy that we used to generate a panel of monoclonal antibodies (mAB) to the endogenous cannabinoid anandamide (N-arachidonylethanolamide, AEA). We designed and successfully prepared a hapten, N-arachidonyl-7-amino-6-hydroxy-heptanoic acid (AHA), which retained the basic characteristic features of anandamide--the carboxamide, the hydroxyl and the lipophilic arachidonyl moiety with its skipped double bond system, while still allowing attachment to protein.

Short-term adolescent nicotine exposure in rats elicits immediate and delayed deficits in T-lymphocyte function: critical periods, patterns of exposure, dose thresholds.

Prenatal nicotine exposure elicits lasting deficiencies in T-lymphocyte mitogenesis, and the period of vulnerability extends into adolescence, the stage at which smoking typically commences. We explored the importance of nicotine exposure patterns (continuous infusion vs. repeated subcutaneous injections), dose-effect relationships, and specificity of the effects.