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.

Background— Little is known about what treatments patients receive after being diagnosed with stable coronary artery disease or what the comparative outcomes are for routine medical treatment (RMT) versus percutaneous coronary intervention (PCI) with RMT for patients in a setting apart from randomized controlled trials. Methods and Results— Patients with stable coronary artery disease undergoing cardiac catheterization in New York State between 2003 and 2008 were followed up to determine the treatment they received. Patients receiving RMT and patients receiving PCI with RMT were propensity matched through the use of 20 factors that could have a bearing on outcomes. The resulting cohort of 933 matched pairs was used to compare mortality/myocardial infarction (MI), mortality, MI, and subsequent revascularization rates. A total of 89% of all patients underwent PCI with RMT. PCI/RMT patients had significantly lower adverse outcome rates at 4 years for mortality/MI (16.5% versus 21.2%; P =0.003), mortality (10.2% versus 14.5%; P =0.02), MI (8.0% versus 11.3%; P =0.007), and subsequent revascularization (24.1% versus 29.1%; P =0.005). Adjusted RMT versus (PCI with RMT) hazard ratios were 1.49 (95% confidence interval, 1.16–1.93) for mortality/MI and 1.46 (95% confidence interval, 1.08–1.97) for mortality. There were no differences for patients ≤65 years of age or for patients with single-vessel disease. Conclusions— Most patients with stable coronary artery disease in New York undergoing catheterization between 2003 and 2008 received PCI. Patients who received PCI experienced lower mortality, mortality/MI, and revascularization rates. The reasons for this finding need to be better understood, including the possible role of low medication adherence rates that have been found in other studies.

AbstractBACKGROUNDSoluble intercellular adhesion molecule 1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.METHODSsICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification (CAC) through year 20 (n = 2378), and both carotid artery stenosis (n = 2432) and intima-media thickness (IMT) at year 20 (n = 2240).RESULTSMedian sICAM-1 was 145.9 μg/L. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% CI 0.003–0.017 mm) higher per SD of sICAM-1 (44 μg/L) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol-lowering medication. With the same adjustment, the odds ratio (OR) for the presence of year-20 carotid artery stenosis per SD of sICAM-1 was 1.12 (95% CI 1.01–1.25, P < 0.04), whereas for occurrence of CAC progression the OR was 1.16 (1.04–1.31, P < 0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.CONCLUSIONSsICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades before the development of clinical CVD.

AbstractOver the past several years, genome‐wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large‐Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large‐scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene‐gene and gene‐environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized.Genet. Epidemiol. 36 : 22–35, 2012. © 2011 Wiley Periodicals, Inc.

Background— The impact of incomplete revascularization (IR) on adverse outcomes after percutaneous coronary intervention remains inconclusive, and few studies have examined mortality during follow-ups longer than 5 years. The objective of this study is to test the hypothesis that IR is associated with higher risk of long-term (8-year) mortality after stenting for multivessel coronary disease. Methods and Results— A total of 13 016 patients with multivessel disease who had undergone stenting procedures with bare metal stents in 1999 to 2000 were identified in the New York State's Percutaneous Coronary Intervention Reporting System. A logistic regression model was fit to predict the probability of achieving complete revascularization (CR) in these patients using baseline risk factors; then, the CR patients were matched to the IR patients with similar likelihoods of achieving CR. Each patient's vital status was followed through 2007 using the National Death Index, and the difference in long-term mortality between IR and CR was compared. It was found that CR was achieved in 29.2% (3803) of the patients. For the 3803 pair-matched patients, the respective 8-year survival rates were 80.8% and 78.5% for CR and IR ( P =0.04), respectively. The risk of death was marginally significantly higher for IR (hazard ratio=1.12; 95% confidence interval, 1.01–1.26, P =0.04). The 95% bootstrap confidence interval for the hazard ratio was 0.98 to 1.32. Conclusions— IR may be associated with higher risk of long-term mortality after stenting with BMS in patients with multivessel disease. More prospective studies are needed to further test this association.

This study examined sex differences in the self-report of depression in early adolecents. A sample of 269 junior high adolescents completed a biographical data sheet, short forms of the Beck Depression Inventory, the Family Environment Scale, a Social Support Index, and a Life Stress Inventory. A subset of 61 mothers completed a Beck inventory, and a Family Environment Scale on their children. Sex differences were demonstrated in the relation of depression to the family and individual variables. Depression in boys was correlated with life stress and lower grades, while for girls, depression was correlated with several types of social support and lower grades.