A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer.

Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer.

Background: The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis, but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.

Methods: In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort, we measured serum estrone, estradiol, and 13 estrogen metabolites, in the 2-, 4-, or 16-hydroxylation pathways, using an LC/MS-MS assay.

Prediagnostic circulating anti-Müllerian hormone concentrations are not associated with prostate cancer risk.

Despite considerable research, the pathogenesis of prostate cancer remains poorly understood. Meanwhile, PSA testing has shifted prostate cancer case populations for study to include a greater proportion of asymptomatic and indolent disease. Thus, efforts to identify prostate cancer biomarkers-particularly for aggressive disease-are required to elucidate pathogenesis and aid screening efficacy.

Association between circulating levels of sex steroid hormones and Barrett's esophagus in men: a case-control analysis.

Background & Aims: Esophageal adenocarcinoma is believed to result from the progression of gastroesophageal reflux disease to erosive esophagitis and re-epithelialization of the esophagus with a columnar cell population termed Barrett's esophagus (BE). Men develop BE and esophageal adenocarcinoma more frequently than women, yet little is known about the mechanisms of this difference. We assessed whether sex steroid hormones were associated with BE in a male population.

Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON).

Background: Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.

Alcohol and the risk of Barrett's esophagus: a pooled analysis from the International BEACON Consortium.

Objectives: Results from studies examining the association between alcohol consumption and the risk of Barrett's esophagus have been inconsistent. We assessed the risk of Barrett's esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett's and Esophageal Adenocarcinoma Consortium.

Methods: For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett's esophagus (cases).

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis.

Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice.

RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB activation, apoptosis, and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal lethality of RIP1-deficient mice. In this study, we generated RIP1 kinase-dead (Ripk1(K45A)) mice and showed they are viable and healthy, indicating that the kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis.

A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry.

Background: Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up.

Metabolic syndrome increases risk of Barrett esophagus in the absence of gastroesophageal reflux: an analysis of SEER-Medicare Data.

Goals: To evaluate the association between metabolic syndrome (MetS) and risk of Barrett esophagus (BE) using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database compared with 2 control groups--Medicare population controls and endoscopy controls.

Background: BE principally arises as an adaptation to the proinflammatory state induced by gastroesophageal reflux disease (GERD). The relationship between obesity and BE is presumed to be mediated by GERD.

Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels.

Probiotic bacteria have gained popularity as a defence against disorders of the bowel. However, the acid sensitivity of these cells results in a loss of viability during gastric passage and, consequently, a loss of efficacy. Probiotic treatment can be supplemented using 'prebiotics', which are carbohydrates fermented specifically by probiotic cells in the body.

Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results.

Background: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.

Methods: In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled.

Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men.

Background: An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.

Methods: We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre).

Understanding the relative importance of preserving functional abilities in Alzheimer's disease in the United States and Germany.

Purpose: To estimate the relative importance that Alzheimer's disease (AD) caregivers in the United States and Germany place on preserving patients' ability to perform activities of daily living.

Methods: US and German residents providing care for a person with AD completed an online preference survey. Each respondent completed five best-worst scaling questions.

Physical activity and sedentary behavior in relation to esophageal and gastric cancers in the NIH-AARP cohort.

Introduction: Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA).

Methods: Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods.

A genome-wide association study of prostate cancer in West African men.

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference.

Investigation of milk proteins binding to the oral mucosa.

High protein dairy beverages are considered to be mouth drying. The drying sensation may be due to the product protein content; however the mechanism of this mouth drying is uncertain. This study investigated the potential adhesion of milk proteins to porcine oral mucosa in vitro.

Childhood height and birth weight in relation to future prostate cancer risk: a cohort study based on the copenhagen school health records register.

Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined.

Comparison of endoscopic therapies and surgical resection in patients with early esophageal cancer: a population-based study.

Background: Outcome data comparing endoscopic eradication therapy (EET) and esophagectomy are limited in patients with early esophageal cancer (EC).

Objective: To compare overall survival and EC-related mortality in patients with early EC treated with EET and esophagectomy.

Design And Setting: Population-based study.

Reading, Mathematics, and Behavioral Difficulties Interrelate: Evidence from a Cross-lagged Panel Design and Population-based Sample.

We examined three questions. First, do reading difficulties increase children's risk of behavior difficulties? Second, do behavioral difficulties increase children's risk of reading difficulties? Third, do mathematics difficulties increase children's risk of reading or behavioral difficulties? We investigated these questions using a sample of 9,324 children followed from third to fifth grade as they participated in a nationally representative dataset, conducting multilevel logistic regression modeling and including statistical control for many potential confounds. Results indicated that poor readers in third grade were significantly more likely to display poor task management, poor self-control, poor interpersonal skills, internalizing behavior problems, and externalizing behavior problems in fifth grade (odds ratio [OR] range = 1.

Regional variations in esophageal cancer rates by census region in the United States, 1999-2008.

Background: Assessment of cancer incidence trends within the U.S. have mostly relied upon Surveillance, Epidemiology, and End Results (SEER) data, with implicit inference that such is representative of the general population.

Optimization and expansion of predictive models for Barrett's esophagus and esophageal adenocarcinoma: could a life-course exposure history be beneficial?

Thrift et al. provide preliminary evidence that younger age of symptomatic gastroesophageal reflux disease exposure is associated with increased risk of Barrett's esophagus. If these findings are confirmed in other studies, the next logical steps are to test whether this, and other age-specific exposures, can help optimize predictive models of Barrett's esophagus and progression to esophageal adenocarcinoma.

Meta-analysis identifies four new loci associated with testicular germ cell tumor.

We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls.

Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies.