Faculty Publications

Context: Family history is a risk factor for many common chronic diseases, yet it remains underutilized in primary care practice. Background: Family Healthware (TM) is a self-administered, web-based tool that assesses familial risk for CHD; stroke; diabetes; and colorectal, breast, and ovarian cancer, and provides a personalized prevention plan based on familial risk. The Family Healthware Impact Trial evaluated the tool. Design: In this cluster RCT, participants completed baseline and 6-month follow-up surveys. The intervention group used Family Healthware directly after the baseline survey. Controls used the tool after completing the follow-up survey. Setting/participants: Patients aged 35-65 years with no known diagnosis of these six diseases were enrolled from 41 primary care practices. Main outcome measures: The prevalence of family-history-based risk for coronary heart disease (CHD); stroke; diabetes; and colorectal, breast, and ovarian cancer was determined in a primary care population. Results: From 2005 to 2007, 3786 participants enrolled. Data analysis was undertaken from September 2007 to March 2008. Participants had a mean age of 50.6 years and were primarily white (91%) women (70%). Of the 3585 participants who completed the risk assessment tool, 82% had a strong or moderate familial risk for at least one of the diseases: CHD (strong=33%, moderate=26%); stroke (strong=15%, moderate=34%); diabetes (strong=11%, moderate=26%); colorectal cancer (strong=3%, moderate=11%); breast cancer (strong=10%, moderate=12%); and ovarian cancer (strong=4%, moderate=6%). Women had a significantly (p<0.04) higher familial risk than men for all diseases except colorectal and ovarian cancer. Overweight participants were significantly (p <= 0.02) more likely to have a strong family history for CHD, stroke, and diabetes. Older participants were significantly (p <= 0.02) more likely to report a strong family history for CHD and stroke as well as colorectal and breast cancer. Conclusions: This self-administered, online tool delineated a substantial burden of family-history-based risk for these chronic diseases in an adult, primary care population. Trial registration: NCT00164658. (Am J Prev Med 2009;36(6):506-514) (C) 2009 American journal of Preventive Medicine

Objectives. Few studies have compared perceptions of risk, worry, severity and control across multiple diseases. This paper examines how these perceptions vary for heart disease, diabetes, stroke, and colon, breast, and ovarian cancers. Methods. The data for this study came from the Family Healthware (TM) Impact Trial (FHITr), conducted in the United States from 2005 to 2007. Healthy adults (N = 2362) from primary care practices recorded their perceptions at baseline for each disease. Analyses were conducted controlling for study site and personal risk factors. Results. Perceived risk was significantly higher for cancers than for other diseases. Men worried most about getting heart disease; women worried most about getting breast cancer. followed by heart disease. Diabetes was perceived to be the least severe condition. Heart disease was perceived to be the most controllable compared to cancers, which were perceived to be the least controllable. Women had higher perceived risk and worry ratings compared to men for several diseases. Conclusions. These data highlight how individuals comparatively view chronic diseases. Addressing prior disease perceptions when communicating multiple disease risks may facilitate an accurate understanding of risk for diseases, and help individuals to effectively identify and engage in relevant behaviors to reduce their risk. (C) 2008 Elsevier Inc. All rights reserved.

Primary cilia are assembled and maintained by evolutionarily conserved intraflagellar transport (IFT) proteins that are involved in the coordinated movement of macromolecular cargo from the basal body to the cilium tip and back. The IF machinery is organized in two structural complexes named complex A and complex B. Recently, inactivation in the mouse germline of Ift genes belonging to complex B revealed a requirement of ciliogenesis, or proteins involved in ciliogenesis, for Sonic Hedgehog (Shh) signaling in mammals. Here we report on a complex A mutant mouse, defective for the Ift122 gene. Ift122-null embryos show multiple developmental defects (exencephaly, situs viscerum inversus, delay in turning, hemorrhage and defects in limb development) that result in lethality. In the node, primary cilia were absent or malformed in homozygous mutant anti heterozygous embryos, respectively. Impairment of the Shh pathway was apparent in both neural tube patterning (expansion of motoneurons and rostro-caudal level-dependent contraction or expansion of the dorso-lateral interneurons), and limb patterning (ectrosyndactyly). These phenotypes are distinct from both complex B IFT mutant embryos and embryos defective for the ciliary protein hennin/Arl13b, and suggest reduced levels of both Gli2/Gli3 activator and Gli3 repressor functions. We conclude that complex A and complex B factors play similar but distinct roles in ciliogenesis and Shh/Gli3 signaling. (C) 2008 Elsevier Inc. All rights reserved.

BACKGROUND: We know very little about how individuals decide to undertake, maintain, or discontinue cancer primary prevention or chemoprevention. PURPOSE: The aims of this article are to (a) examine whether and, if so, how traditional health behavior change models are relevant for decision making in this area; (b) review the application of decision aids to forming specific, personal choices between options; and (c) identify the challenges of evaluating these decision processes to suggest areas for future research. METHODS: Theoretical models and frameworks derived from the health behavior change and decision-making fields were applied to cancer primary prevention choices. Decision aids for the human papillomavirus (HPV) vaccine, Hormone Replacement Therapy (HRT), and tamoxifen were systematically examined. RESULTS: Traditional concepts such as decisional balance and cues to action are relevant to understanding cancer primary prevention choices; Motivational Interviewing, Self-Determination Theory, and the Preventive Health Model may also explain the facilitators of decision making. There are no well-tested HPV vaccine decision aids, although there have been some studies on aids for HPV testing. There are several effective decision aids for HRT and tamoxifen; evidence-based decision aid components have also been identified. CONCLUSIONS: Additional theory-based empirical research on decision making in cancer primary prevention and chemoprevention, particularly at the interface of psychology and behavioral economics, is suggested.

We have previously reported the identification and characterization of a novel BRCA1/2 interacting protein complex, BRCC (BRCA1/2-containing complex). BRCC36, one of the proteins in BRCC, directly interacts with BRCA1, and regulates the ubiquitin E3 ligase activity of BRCC. Importantly, BRCC36 is aberrantly expressed in the vast majority of breast tumors, indicating a potential role in the pathogenesis of this disease. To further elucidate the functional consequence of abnormal BRCC36 expression in breast cancer, we have done in vivo silencing studies using small interfering RNAs targeting BRCC36 in breast cancer cell lines, i.e., MCF-7, ZR-75-1, and T47D. Knock-down of BRCC36 alone does not affect cell growth, but when combined with ionizing radiation (IR) exposure, it leads to an increase in the percentage of cells undergoing apoptosis when compared with the small interfering RNA control group in breast cancer cells. Immunoblot analysis shows that inhibition of BRCC36 has ! no effect on the activation of ATM, expression of p21 and p53, or BRCA1/BARD1 interaction following IR exposure. Importantly, BRCC36 depletion disrupts IR-induced phosphorylation of BRCA1. Immunofluorescent staining of BRCA1 and gamma-H2AX indicates that BRCC36 depletion prevents the formation of BRCA1 nuclear foci in response to DNA damage in breast cancer cells. These results show that down-regulation of BRCC36 expression impairs the DNA repair pathway activated in response to IR by inhibiting BRCA1 activation, thereby sensitizing breast cancer cells to IR-induced apoptosis.

The Behavioral Oncology Interest Group of the American Society of Preventive Oncology held a Roundtable session on March 10, 2002, at the American Society of Preventive Oncology annual meeting in Bethesda, Maryland, to discuss the current state-of-the-science in behavioral approaches to cancer prevention and control and to delineate priorities for additional research. Four key areas were considered: (a) behavioral approaches to cancer genetic risk assessment and testing; (b) biological mechanisms of psychosocial effects on cancer; (c) the role of risk perceptions in cancer screening adherence; and (d) the impact of tailored and targeted interventions on cancer prevention and control research. The evidence reviewed indicates that behavioral approaches have made significant contributions to cancer prevention and control research. At the same time, there is a need to more closely link future investigations to the underlying base of behavioral science principles and paradigms th! at guide them. To successfully bridge the gap between the availability of effective new cancer prevention and control technologies and the participants they are meant to serve will require the development of more integrative conceptual models, the incorporation of more rigorous methodological designs, and more precise identification of the individual and group characteristics of the groups under study.