Citations

Abstract Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07–1.27; P = 7.42 × 10−4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73–0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94–1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05–1.29; P = 3.8 × 10−4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10–1.52; P = 1.8 × 10−3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645–57. ©2012 AACR.

Abstract:Post‐transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme‐linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False‐positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis.

Abstract In April 2010, a NIH workshop was convened to discuss the current state of understanding of lung cell plasticity, including the responses of epithelial cells to injury, with the objectives of summarizing what is known, what the field needs to know, and how to get there. The proximal stimulus for this workshop is the body of recent evidence suggesting that plasticity is a prominent but incompletely characterized property of lung epithelial cells, and that a focus on understanding this aspect of epithelial cell biology in particular, may be an important window into disease pathobiology and pathogenesis. In addition to their many vital functions in maintaining tissue homeostasis, epithelial cells have emerged as both a central target of disease initiation and an active contributor to disease progression, making a workshop to investigate the role of cell plasticity in lung injury and repair timely. The workshop was organized around four major themes: lung epithelial cell plasticity, signaling control of plasticity, fibroblast plasticity and crosstalk, and translation to human disease. Although this breakdown was recognized to be somewhat artificial, it was felt that this approach would promote cross-fertilization among groups that ordinarily do not communicate and lend itself to the generation of new approaches. The summary reports of individual group discussions below are followed by consensus priorities and recommendations of the workshop participants.

ABSTRACT Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans , C. tropicalis , and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata , non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata , ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender.