The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.

BACKGROUND: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. METHODS: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. RESULTS: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. CONCLUSIONS: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. IMPACT: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR.

Pilot comparative effectiveness study of surface perturbation treadmill training to prevent falls in older adults.

BACKGROUND: Falls are the leading cause of fatal and non-fatal injuries among older adults. Exercise programs appear to reduce fall risk, but the optimal type, frequency, and duration of exercise is unknown. External perturbations such as tripping and slipping are a major contributor to falls, and task-specific perturbation training to enhance dynamic stability has emerged as a promising approach to modifying fall risk. The purpose of this pilot study was 1) to determine the feasibility of conducting a large pragmatic randomized trial comparing a multidimensional exercise program inclusive of the surface perturbation treadmill training (SPTT) to multidimensional exercise alone (Standard PT); and 2) to assess fall outcomes between the two groups to determine whether an effect size large enough to warrant further study might be present. METHODS: A randomized pilot study at two outpatient physical therapy clinics. Participants were over age 64 and referred for gait and balance training. Feasibility for a larger randomized trial was assessed based on the ability of therapists to incorporate the SPTT into their clinical practice and acceptance of study participation by eligible patients. Falls were assessed by telephone interview 3 months after enrollment. RESULTS: Of 83 patients who were screened, 73 met inclusion criteria. SPTT was successfully adapted into clinical practice and 88% of eligible subjects were willing to be randomized, although 10% of the SPTT cohort dropped out prior to treatment. The SPTT group showed fewer subjects having any fall (19.23% vs. 33.33% Standard PT; p < 0.227) and fewer having an injurious fall (7.69% vs. 18.18%; p < 0.243). These results were not statistically significant but this pilot study was not powered for hypothesis testing. CONCLUSIONS: Physical therapy inclusive of surface perturbation treadmill training appears clinically feasible, and randomization between these two PT interventions is acceptable to the majority of patients. These results appear to merit longer-term study in an adequately powered trial. TRIAL REGISTRATION: clinicaltrials.gov: NCT01006967.