Citations

Background— Fibromuscular dysplasia (FMD), a noninflammatory disease of medium-size arteries, may lead to stenosis, occlusion, dissection, and/or aneurysm. There has been little progress in understanding the epidemiology, pathogenesis, and outcomes since its first description in 1938. Methods and Results— Clinical features, presenting symptoms, and vascular events are reviewed for the first 447 patients enrolled in a national FMD registry from 9 US sites. Vascular beds were imaged selectively based on clinical presentation and local practice. The majority of patients were female (91%) with a mean age at diagnosis of 51.9 (SD 13.4 years; range, 5–83 years). Hypertension, headache, and pulsatile tinnitus were the most common presenting symptoms of the disease. Self-reported family history of stroke (53.5%), aneurysm (23.5%), and sudden death (19.8%) were common, but FMD in first- or second-degree relatives was reported only in 7.3%. FMD was identified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and vertebral arteries in 82 patients. A past or presenting history of vascular events were common: 19.2% of patients had a transient ischemic attack or stroke, 19.7% had experienced arterial dissection(s), and 17% of patients had an aneurysm(s). The most frequent indications for therapy were hypertension, aneurysm, and dissection. Conclusions— In this registry, FMD occurred primarily in middle-aged women, although it presents across the lifespan. Cerebrovascular FMD occurred as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis.

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 The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.

Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.

ABSTRACTWe report an unusual case of extraintestinal infection with adultEnterobius vermicularisworms in the nares and ocular orbit of a 14-year-old girl in Illinois. Only one other similar case has been reported in the English-language literature.

ABSTRACT Blastomyces dermatitidis and Histoplasma capsulatum are dimorphic fungi that often cause self-limited respiratory infections. However, they may also cause severe disseminated disease, depending on the level of the exposure to the organism and the host immune status. In addition, patients with infections caused by these fungi may have very similar clinical presentations. Although microbiologic culture is a standard method for detecting these pathogens, their recovery may require days to weeks, and the manipulation of cultures presents a significant safety hazard to laboratory personnel. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect and differentiate B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens. Primers and fluorescence resonance energy transfer hybridization probes were designed to target the histidine kinase and glyceraldehyde-3-phosphate dehydrogenase genes of B. dermatitidis and H. capsulatum , respectively. The analytical sensitivity of the assay was determined to be 100 copies/μl for both fungi. From culture isolates, the assay demonstrated 100% specificity and 100% sensitivity for B. dermatitidis and 100% specificity and 94% sensitivity for H. capsulatum . Detection directly from 797 clinical specimens demonstrated specificities and sensitivities of 99% and 86% for B. dermatitidis and 100% and 73% for H. capsulatum compared with the results for culture. This real-time PCR assay provides a rapid method for the detection of B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens.