Preventing Chronic Disease

ESSAY Suggested citation for this article: Abstract Colorectal cancer is the second leading cause of cancerrelated mortality among U.S. adults. In 2004, treatment costs for colorectal cancer were $8.4 billion. There is substantial evidence that colorectal cancer incidence and mortality are reduced with regular screening. The natural history of this disease is also well described: most colorectal cancers develop slowly from preexisting polyps. This slow development provides an opportunity to intervene with screening tests, which can either prevent colorectal cancer through the removal of polyps or detect it at an early stage. However, much less is known about how best to implement an effective colorectal cancer screening program. Screening rates are low, and uninsured persons, low-income persons, and persons who have not visited a physician within a year are least likely to be screened. This article describes briefly this demonstration program and the process CDC used to design it and to select program sites. The multiple-methods evaluation now under way to assess the program's feasibility and describe key outcomes is also detailed. Evaluation results will be used to inform future activities related to organized screening for colorectal cancer

De novo missense variants in FBXW11 cause diverse developmental phenotypes including brain, eye and digit anomalies

The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11 variants identified by whole exome or whole genome sequencing and not reported in the gnomAD database. Their phenotypes include striking neurodevelopmental, digital, jaw, and eye anomalies, and in one individual, features resembling Noonan syndrome, a condition caused by dysregulated RAS signaling. FBXW11 encodes an F-box protein, part of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex, involved in ubiquitination and proteasomal degradation and thus fundamental to many protein regulatory processes. FBXW11 targets include b-catenin and GLI transcription factors, key mediators of Wnt and Hh signaling, respectively, critical to digital, neurological, and eye development. Structural analyses indicate affected residues cluster at the surface of the loops of the substrate-binding domain of FBXW11, and the variants are predicted to destabilize the protein and/or its interactions. In situ hybridization studies on human and zebrafish embryonic tissues demonstrate FBXW11 is expressed in the developing eye, brain, mandibular processes, and limb buds or pectoral fins. Knockdown of the zebrafish FBXW11 orthologs fbxw11a and fbxw11b resulted in embryos with smaller, misshapen, and underdeveloped eyes and abnormal jaw and pectoral fin development. Our findings support the role of FBXW11 in multiple developmental processes, including those involving the brain, eye, digits, and jaw

Life cycle of television public service announcements disseminated through donated airtime

Objective: To investigate the longevity and reach of television public service announcements (PSAs) developed by the Centers for Disease Control and Prevention's Screen for Life: National Colorectal Cancer Action Campaign. Methods: Television airtime donated to Screen for Life PSAs was tracked, and the impressions (a broadcasting metric for audience size) generated by PSAs in circulation ≥5 years were analyzed in 2014. The sample consisted of 8 PSAs, including English and Spanish PSAs, PSAs featuring celebrities, and PSAs redistributed multiple times after their initial release. Results: During the most recent year of circulation (5–9 years after initial release), each PSA generated 15.7 million to 251.7 million impressions. Peak annual impressions were achieved as late as 9 years after a PSA's initial release. When PSAs were redistributed 2 years or longer after the prior distribution, annual impressions increased over the preceding year by >20 million in 80.0% of instances. Among English PSAs, those featuring celebrities produced the highest mean and peak annual impressions. Conclusions: Donated-placement television PSAs can be a long-lived health promotion strategy. Redistribution may enhance PSA longevity, and featuring celebrities, particularly in English PSAs, may expand reach