International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Improving Screening Uptake among Breast Cancer Survivors and Their First-Degree Relatives at Elevated Risk to Breast Cancer: Results and Implications of a Randomized Study in the State of Georgia

Women diagnosed with breast cancer at a relatively early age (&le;45 years) or with bilateral disease at any age are at elevated risk for additional breast cancer, as are their female first-degree relatives (FDRs). We report on a randomized trial to increase adherence to mammography screening guidelines among survivors and FDRs. From the Georgia Cancer Registry, breast cancer survivors diagnosed during 2000&ndash;2009 at six Georgia cancer centers underwent phone interviews about their breast cancer screening behaviors and their FDRs. Nonadherent survivors and FDRs meeting all inclusion criteria were randomized to high-intensity (evidence-based brochure, phone counseling, mailed reminders, and communications with primary care providers) or low-intensity interventions (brochure only). Three and 12-month follow-up questionnaires were completed. Data analyses used standard statistical approaches. Among 1055 survivors and 287 FDRs who were located, contacted, and agreed to participate, 59.5% and 62.7%, respectively, reported breast cancer screening in the past 12 months and were thus ineligible. For survivors enrolled at baseline (N = 95), the proportion reporting adherence to guideline screening by 12 months post-enrollment was similar in the high and low-intensity arms (66.7% vs. 79.2%, p = 0.31). Among FDRs enrolled at baseline (N = 83), screening was significantly higher in the high-intensity arm at 12 months (60.9% vs. 32.4%, p = 0.03). Overall, about 72% of study-eligible survivors (all of whom were screening nonadherent at baseline) reported screening within 12 months of study enrollment. For enrolled FDRs receiving the high-intensity intervention, over 60% reported guideline screening by 12 months. A major conclusion is that using high-quality central cancer registries to identify high-risk breast cancer survivors and then working closely with these survivors to identify their FDRs represents a feasible and effective strategy to promote guideline cancer screening