Citations

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Purpose To compare magnetic resonance imaging (MRI) and computed tomography (CT) with each other and to International Federation of Gynecology and Obstetrics (FIGO) clinical staging in the pretreatment evaluation of early invasive cervical cancer, using surgicopathologic findings as the reference standard. Patients and Methods This prospective multicenter clinical study was conducted by the American College of Radiology Imaging Network and the Gynecologic Oncology Group from March 2000 to November 2002; 25 United States health centers enrolled 208 consecutive patients with biopsy-confirmed cervical cancer of FIGO stage ≥ IB who were scheduled for surgery based on clinical assessment. Patients underwent FIGO clinical staging, helical CT, and MRI. Surgicopathologic findings constituted the reference standard for statistical analysis. Results Complete data were available for 172 patients; surgicopathologic findings were consistent with FIGO stages IA to IIA in 76% and stage ≥ IIB in 21%. For the detection of advanced stage (≥ IIB), sensitivity was poor for FIGO clinical staging (29%), CT (42%), and MRI (53%); specificity was 99% for FIGO clinical staging, 82% for CT, and 74% for MRI; and negative predictive value was 84% for FIGO clinical staging, 84% for CT, and 85% for MRI. MRI (area under the receiver operating characteristic curve [AUC], 0.88) was significantly better than CT (AUC, 0.73) for detecting cervical tumors (P = .014). For 85% of patients, FIGO clinical staging forms were submitted after MRI and/or CT was performed. Conclusion CT and MRI performed similarly; both had lower staging accuracy than in prior single-institution studies. Accuracy of FIGO clinical staging was higher than previously reported. The temporal data suggest that FIGO clinical staging was influenced by CT and MRI findings.