Purpose-As direct to consumer (DTC) genetic testing becomes more available, a diverse group of consumers, including those with limited health literacy, may consider testing. In light of concerns raised about DTC genetic testing, this study sought to critically examine whether the informational content, literacy demands, and usability of health-related DTC websites met existing recommendations.Methods-A content analysis was performed on 29 health-related DTC websites. Two coders independently evaluated each website for informational content (e.g., benefits, limitations), literacy demands (e.g., reading level), and usability (e.g., ease of navigation).Results-Most sites presented health conditions and some markers for which they tested, benefits of testing, a description of the testing process, and their privacy policy. Fewer cited scientific literature, explained test limitations or provided an opportunity to consult a health professional. Key informational content was difficult to locate on most sites. Few sites gave sample disease risk estimates, or used common language and explained technical terms consistently. Average reading level was grade 15.Conclusion-The quality of informational content, literacy demands, and usability across health-related DTC websites varied widely. Many users would struggle to find and understand the important information. In order for consumers to better understand the content on these sites and evaluate the meaning of the tests for their health, sites should lower the demands placed on users by distilling and prioritizing the key informational content while simultaneously attending to the reading level and usability elements. In the absence of regulation compelling such changes, government agencies or professional organizations may need to increase consumer and provider awareness of these issues.

Background and Aims-Clinical genetic testing can help direct cancer screening for members of Lynch Syndrome families; however there is limited information about family communication of genetic test results.

Background Lynch Syndrome (LS) is a hereditary cancer syndrome which conveys a high risk of colorectal cancer (CRC). Guidelines recommend colonoscopy every 1–2 years. There is limited information about screening compliance in this high risk group. Methods Data about cancer screening behaviors were obtained from subjects recruited through 4 U.S. cancer genetics clinics. The main outcome was prevalence of appropriate CRC surveillance for LS. Results 181 individuals had a family history that met Amsterdam Criteria for LS (n=154) and/or had an identified mutation in a mismatch repair (MMR) gene (n=105). 132/181 (73%) had appropriate LS surveillance with colonoscopies at least every 2 years for individuals age ≥25. Of those with inadequate surveillance, 26/49 (53%) had colonoscopies at 3–5 year intervals. There were no significant differences in health care setting, perceived risk of CRC, or compliance with screening for other cancers. Rates of appropriate surveillance were higher among individuals who had been referred for genetic evaluation for LS compared to those who had not (109/136 (80%) vs 23/45 (51%), respectively p=0.0004). In multivariate analysis, personal history of CRC (OR 2.81), having a first degree relative with CRC at age<50 (OR 2.61), and having undergone a genetic evaluation (OR 4.62) were associated with appropriate CRC surveillance for LS. Conclusions The time between colonoscopic exams in patients with LS is often longer than recommended by current guidelines and may place them at risk for interval cancers. Recognizing clinical features of LS and providing genetic counseling, evaluation, and intensive surveillance may improve cancer prevention for those at highest risk for CRC.

mobilization in these cells is dose-dependently inhibited by NOR-1 (an NO donor). This inhibition was prevented by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-CPT-cGMPS (an inhibitor of protein kinase G). Treatment of endothelial cells with 8-bromo-cGMP reduced ET-1-induced Ca 2ϩ mobilization in a manner similar to that observed with NOR-1 treatment. In addition, NOR-1 or cGMP reduced Ca 2ϩ mobilization induced by mastoparan (an activator of G protein), inositol 1,4,5-trisphosphate, or thapsigargin (an inhibitor of Ca 2ϩ -ATPase). Interestingly, alterations in endothelial cytoskeleton (actin and vimentin) were associated with these effects. The data indicate for the first time that the cGMP-dependent protein kinase colocalizes with actin. These changes were accompanied by altered levels of phosphorylated vasodilator-stimulated phosphoprotein, which were elevated in endothelial cells incubated with NOR-1 and significantly reduced by ODQ or Rp-8-CPTcGMPS. The findings indicate a potential mechanism by which the functional interrelationship between ET-1 and NO plays a role in regulating capillary tone, microcirculation, and blood-brain barrier function. capillary endothelium; endothelin-1; nitric oxide; calcium mobilization; cytoskeleton THE CENTRAL MICROCIRCULATORY BED (composed of small arteries, capillaries, and venules) is the main intermediary structure responsible for maintaining the cellular homeostasis in the brain. Its regulatory functions principally reside within the endothelium, which consists of a single layer of flat cells. In microvessels, the endothelium forms a continuous inner lining, whereas in the capillaries it provides a single cellular barrier between the blood and brain. These endothelial cells (EC) express a variety of biological activities, including the control of vascular tone and blood flow through the Address for reprint requests and other correspondence: R. M. McCarron,

Previous studies have identified low patient accrual in largescale cancer clinical trials, particularly for underrepresented groups, such as ethnic minorities, females, and patients >65 years. As there have been few studies examining participation in cancer genetics epidemiologic research, our objective was to identify clinical and demographic factors predicting enrollment in these studies. A total of 1,111 patients diagnosed with colorectal cancer presenting to a gastrointestinal oncology clinic were approached to enroll in a study investigating the role of the MSH6 gene in familial colorectal cancer. Patient consent was sought for providing a blood specimen for DNA analysis and review of medical records/ tumor specimens and contacting family members to confirm the family history of cancer. Seven predictor variables for enrollment (age, sex, ethnicity, family history of colorectal cancer in a first-degree relative, presence of children, insurance type, and type of visit) were analyzed using logistic regression analysis to determine the effect on decision to enroll. Of 1,111 patients approached, 696 (62.6%) enrolled in the study. Of these approached individuals, 4.2% were of nonwhite ethnicity and 33.5% were age z65 years. Patients of white ethnicity [odds ratio (OR), 2.10; P = 0.018], males (OR, 1.47; P = 0.002), those ages V65 years (OR, 1.42; P = 0.009), and those with a first-degree relative with colorectal cancer (OR, 1.57; P = 0.005) were significantly more likely to enroll. Fewer than 4% of all participants denied permission for the study researchers to access information from medical records or to be recontacted by researchers to discuss the enrollment of additional family members. Our data suggest that, once subjects decided to enroll, the majority (88%) was comfortable with consenting to all study components, including the creation of cell lines and future recontact. Low participation rates for ethnic minorities, females, and elderly patients are similar for both cancer genetics and clinical trial studies. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1355 -9)

A B S T R A C T PurposeLynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. Patients and MethodsA total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. ResultsOf the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as "high" or "very high" compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome-associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. ConclusionPatients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.

Objective-Causal beliefs about cancer may influence preventive behaviors and medical care. We examined the relationship between beliefs about causation for lung, colon, and skin cancer and the use of lay interpersonal sources of health information (community organizations, family, friends). Results-About 40% of respondents reported that community organizations provided them with health information, while 15% discussed health information "very frequently" with their family or friends. In multivariate models, individuals who never spoke with family or friends about health were more likely to believe that colon cancer risk is not modifiable; those provided with health information by community organizations were less likely to believe that skin cancer risk is not modifiable. Speaking with family or friends about health was also associated with endorsing the belief that skin cancer is caused by behavior or lifestyle. Methods-DataConclusion-These findings showed that lay interpersonal health information sources are associated with beliefs about the modifiability of colon and skin cancer risk. Future research is needed to investigate whether and how such information sources might influence decisions about engaging in preventive behaviors.

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