|
| ||
|
|
||
Case Status (case + status)
Selected AbstractsRemoval of benzo(a)pyrene diol epoxide (BPDE)-DNA adducts as a measure of DNA repair capacity in lymphoblastoid cell lines from sisters discordant for breast cancerENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2002Grazyna Motykiewicz Abstract The mutagen sensitivity assay is one of the approaches used to investigate individual DNA repair capacity. This method is based on the premise that after in vitro treatment with a test mutagen, DNA from subjects with defective repair will be more damaged than DNA from those with an efficient repair system. However, very little is known about unmeasured processes that occur between cell treatment and final assessment of DNA damage. To develop a more precise assay, we modified the traditional mutagen sensitivity assay to also include measurement of DNA damage after culturing cells in the absence of mutagen. First, we treated apparently normal and xeroderma pigmentosum lymphoblastoid cell lines with various doses of benzo(a)pyrene diol epoxide (BPDE) and harvested cells at different time points. A polyclonal antiserum against BPDE-DNA was used to quantitate levels of adducts by immunoslot-blot and immunohistochemistry. Selected conditions included treatment with 10 ,M BPDE, a 4-hr culture in mutagen-free medium, and immunohistochemical measurement of BPDE-DNA adducts. The method was then applied in a pilot study to 50 lymphoblastoid lines from sisters discordant for breast cancer. There was no significant difference between cases and controls in the level of BPDE-DNA adducts in lymphoblasts harvested immediately after BPDE treatment. However, after a 4-hr culture in mutagen-free medium, the level of adducts was significantly higher (P = 0.006) among cases than in controls. There was a two-fold increase in mean adduct removal in lines from nonaffected as compared to affected sisters (44% and 22% decrease, respectively). DNA repair capacity was predictive of case status (P = 0.04) in logistic regression analysis. This method, which can be easily applied to large numbers of samples, should be useful in studies to investigate the role of DNA repair in cancer risk. Environ. Mol. Mutagen. 40:93,100, 2002. © 2002 Wiley-Liss, Inc. [source] Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ,pleasurable buzz' during early experimentation with smokingADDICTION, Issue 9 2008Richard Sherva ABSTRACT Aims To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes. Design, setting, participants Case,control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls). Measurements Cases had smoked , five cigarettes/day for , 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study. Findings A non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001). Conclusions We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence. [source] An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitusPEDIATRIC DIABETES, Issue 8 2009M Simpson Aims: To determine whether Glo-3A, (formerly referred to as homologue of Glb1 or Glb1) antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D) and to investigate their relation with environmental correlates of T1D. Methods: We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma-associated antigen-2 (IA-2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glo-3A by ELISA. Results: Adjusting for family history of T1D and human leukocyte antigen (HLA)-DR4 positivity, Glo-3A antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99,1.03). Adjusting for age, family history of T1D, and HLA-DR4 positivity, Glo-3A antibody levels were inversely associated with breast-feeding duration (beta = ,0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glo-3A antibody levels in cases (beta = 0.73, p = 0.003) but not in controls. Conclusion: Differing correlates of Glo-3A antibodies in IA cases and controls suggest an underlying difference in mucosal immune response. [source] Geographic distribution of autism in California: A retrospective birth cohort analysis,AUTISM RESEARCH, Issue 1 2010Karla C. Van Meter Abstract Prenatal environmental exposures are among the risk factors being explored for associations with autism. We applied a new procedure combining multiple scan cluster detection tests to identify geographically defined areas of increased autism incidence. This procedure can serve as a first hypothesis-generating step aimed at localized environmental exposures, but would not be useful for assessing widely distributed exposures, such as household products, nor for exposures from nonpoint sources, such as traffic. Geocoded mothers' residences on 2,453,717 California birth records, 1996,2000, were analyzed including 9,900 autism cases recorded in the California Department of Developmental Services (DDS) database through February 2006 which were matched to their corresponding birth records. We analyzed each of the 21 DDS Regional Center (RC) catchment areas separately because of the wide variation in diagnostic practices. Ten clusters of increased autism risk were identified in eight RC regions, and one Potential Cluster in each of two other RC regions. After determination of clusters, multiple mixed Poisson regression models were fit to assess differences in known demographic autism risk factors between the births within and outside areas of elevated autism incidence, independent of case status. Adjusted for other covariates, the majority of areas of autism clustering were characterized by high parental education, e.g. relative risks >4 for college-graduate vs. nonhigh-school graduate parents. This geographic association possibly occurs because RCs do not actively conduct case finding and parents with lower education are, for various reasons, less likely to successfully seek services. [source] | ||||||||||