Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due to Lynch Syndrome?

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS. HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients. METHODS: 253 individuals with an MMRD CRC or EC who underwent genetic counseling at one institution were included in analysis in 1 of 4 groups: LS, MMRD+/germline-, MMRD+/VUS, sporadic MSI-H (MMRD tumor with MLH1 promoter hypermethylation or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM1,2,6. Kruskal-Wallis tests were used to compare family history scores. Logistic regression was used to determine what factors were predictive of LS. RESULTS: MMRD+/germline- individuals had significantly lower median family history scores (PREMM1,2,6=7.3, MMRpro=8.1) than LS individuals (PREMM1,2,6=26.1, MMRpro=89.8, p CONCLUSION: MMRD+/germline- individuals have less suggestive family histories of LS than individuals with LS, but more suggestive family histories than sporadic MSI-H individuals. CRC and/or EC patients with abnormal tumor studies are more likely to have a germline LS mutation if they have a family history suggestive of hereditary cancer. These results imply that the MMRD+/germline- group may not all have LS. This finding highlights the need to determine other somatic, epigenetic or germline causes of MMRD tumors so that these patients and their families can be accurately counseled regarding screening and management.

ATTITUDES AND PRACTICES OF GENETIC COUNSELORS IN PROVIDING PREDICTIVE TESTING TO MINORS AT RISK FOR LI-FRAUMENI SYNDROME

Li- Fraumeni Syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome caused by mutations in the TP53 gene that predisposes individuals to a wide variety of cancers, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, and adrenocortical carcinomas. Individuals found to carry germline mutations in TP53 have a 90% lifetime cancer risk, with a 20% chance to develop cancer under the age of 20. Despite the significant risk of childhood cancer, predictive testing for unaffected minors at risk for LFS historically has not been recommended, largely due to the lack of available and effective screening for the types of cancers involved. A recently developed screening protocol suggests an advantage to identifying and screening children at risk for LFS and we therefore hypothesized that this alongside with the availability of new screening modalities may substantiate a shift in recommendations for predictive genetic testing in minors at risk for LFS. We aimed to describe current screening recommendations that genetic counselors provide to this population as well as explore factors that may have influenced genetic counselors attitude and practice in regards to this issue. An online survey was emailed to members of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). Of an estimated 1000 eligible participants, 172 completed surveys that were analyzed. Genetic counselors in this study were more likely to support predictive genetic testing for this population as the minor aged (p

Baseline quality of life as a predictor of exercise intervention adherence among endometrial cancer survivors

Background: The objective of this analysis is to test whether baseline quality of life (QOL) measurements, body mass index (BMI) and prior exercise behavior are significantly associated with (1) telephone counseling adherence, and (2) activity at the final assessment, in a physical activity promoting intervention among endometrial cancer survivors.^ Methods: One hundred endometrial cancer survivors not currently meeting physical activity guidelines completed baseline QOL and anthropometric assessments to measure general physical and mental health [Medical Outcomes Survey (SF-36)], sleep patterns and sleep quality [Pittsburgh Sleep Quality Index (PSQI)], perceived stress [Perceived Stress Scale (PSS)], cancer-specific concerns of long-term survivors [Quality of Life in Adult Cancer Survivors (QLACS)], and psychological distress [Brief Symptom Inventory-18 (BSI-18)]. Survivors were counseled by telephone during the 6-month intervention and their completion rate determined their adherence. The primary variables of interest included age, baseline BMI, baseline activity level, time since diagnosis, education, treatment received, and the SF-36 physical and mental component scores.^ Results: Final activity was most closely linked with baseline activity (p<.001) and less invasive surgery, being leaner and older, and experiencing less pain and more vitality. Telephone counseling was also predicted well by baseline activity, working less and having better overall cancer-related functioning.^ Conclusion: Above and beyond the QOL measures, baseline activity was the strongest predictor of both final activity and telephone counseling adherence. While education, surgery treatment type and bodily pain were important predictors for final exercise and employment status and cancer-related quality of life were important predictors for telephone counseling adherence, considering adaptive exercise interventions that focus heavily on engaging inactive participants may be a way to produce better exercise-related outcomes in the endometrial cancer survivor population.^

The effects of adequacy and content of prenatal care on birth outcomes in a high -risk Missouri population

The purpose of this observational study was investigation of the relationship between quantitative adequacy of prenatal care, specific prenatal care content and pregnancy outcome in a high risk Missouri population. A sample of 1484 women from three Missouri regions known to have high rates of low birth weight, infant mortality, and inadequate prenatal care rates participated in structured post-partum interviews. Approximately one-half of the sample had received adequate prenatal care and the other half inadequate prenatal care as determined by an index utilized by the Missouri Department of Health.^ Prenatal care content was assessed by reports of prenatal education in six different areas: Diet, smoking, alcohol, drug, preterm labor counseling, and advice on when to call the health provider if preterm labor was suspected by the woman. Low birth weight, in both term and preterm infants, were the two birth outcomes examined. A variety of maternal socio-demographic variables were also considered.^ The results of this study suggest that specific educational content, delivered during prenatal care, may have lessen the risk of giving birth to a preterm-low birth weight infant. Prenatal education for recognition of preterm labor, and advice on when to call the health provider if preterm labor was suspected were found to be associated with a decreased risk of preterm delivery. Specific educational content was not, however, associated with risk of term-low weight birth nor was quantitative adequacy of care associated with the risk of either term- or preterm-low birth weight.^ These findings reinforce a body of literature which stresses the importance of appropriate prenatal care in preventing preterm low birth weight. Additionally, the findings suggest interventions that may be specifically effective for prematurity prevention. ^

Cost -effectiveness of services and treatments for ambulatory dually diagnosed CMHC clients: Implications for managed care

This paper reports a cost-effectiveness analysis of standard therapeutic interventions received by ambulatory dually diagnosed clients of a Community Mental Health Center (CMHC). For the purposes of this study dually diagnosed was defined as a DSM-III-R or IV diagnosis of a major mental disorder and a concomitant substance abuse disorder. The prevalence of dually diagnosed people among the mentally ill and their unique and problematic nature continues to challenge and encumber CMHCs and poses grave public health risks. An absence of research on these clients in community-based settings and the cost-effectiveness of their standard CMHC care has hindered the development of effective community-based intervention strategies. This exploratory and descriptive effort is a first step toward providing information on which to base programmatic management decisions.^ Data for this study were derived from electronic client records of a CMHC located in a large Southwestern, Sun-belt metropolitan area. A total of 220 records were collected on clients consecutively admitted during a two-and-one-half year period. Information was gathered profiling the clients' background characteristics, receipt of standard services and treatments, costs of the care they received, and length of CMHC enrollment and subsequent psychiatric hospitalizations. The services and treatments were compared with regard to their costs and predicted contributions toward maintaining clients in the community and out of public psychiatric hospitals.^ This study investigated: (1) the study groups' background, mental illness, and substance abuse characteristics; (2) types, extent, and patterns of their receipt of standard services and treatments; (3) associations between the receipt of services and treatments, community tenure, and risk of psychiatric hospitalization; and, (4) comparisons of average costs for services and treatments in terms of their contributions toward maintaining the clients in the community.^ The results suggest that substance abuse and other lifestyle factors were related to the dually diagnosed clients' admissions to the CMHC. The dually diagnosed clients' receipt of care was associated strongly with their insurability and global functioning. Medication Services were the most expensive yet effective service or treatment. Supported Education was the third most expensive and second most effective. Psychosocial Services, the second most expensive, were only effective in terms of maintaining clients in the community. Group Counseling, the fourth most expensive, had no effect on community maintenance and increased the risk of hospitalization when accompanied by Medication Services. Individual Counseling, the least expensive, had no effect on community maintenance. But it reduced the risk of hospitalization when accompanied by Medication Services. Networking/Referral, the fifth most expensive service or treatment, was ineffective.^ The study compared the results with findings in the literature. Implications are discussed regarding further research, study limitations, practical applications and benefits, and improvements to theoretical understandings, in particular, concepts underscoring Managed Care. ^

Planning, implementation, and evaluation of an HIV -screening program for pregnant women

The purpose of this study was to evaluate the effectiveness of an HIV-screening program at a private health-care institution where the providers were trained to counsel pregnant women about the HIV-antibody test according to the latest recommendations made by the U.S. Public Health Service (PHS) and the Texas legislature. A before-and-after study design was selected for the study. The participants were OB/GYN nurses who attended an educational program and the patients they counseled about the HIV test. Training improved the nurses' overall knowledge about the content of the program and nurses were more likely to offer the HIV test to all pregnant women regardless of their risk of infection. Still, contrary to what was predicted, the nurses did not give more information to increase the knowledge pregnant women had about HIV infection, transmission, and available treatments. Consequently, many women were not given the chance to correctly assess their risk during the counseling session and there was no evidence that knowledge would reduce the propensity of many women to deny being at risk for HIV. On the other hand, pregnant women who received prenatal care after the implementation of the HIV-screening program were more likely to be tested than women who received prenatal care before its implementation (96% vs. 48%); in turn, the likelihood that more high-risk women would be tested for HIV also increased (94% vs. 60%). There was no evidence that mandatory testing with right of refusal would deter women from being tested for HIV. When the moment comes for a woman to make her decision, other concerns are more important to her than whether the option to be tested is mandatory or not. The majority of pregnant women indicated that their main reasons for being tested were: (a) the recommendation of their health-care provider; and (b) concern about the risks to their babies. Recommending that all pregnant women be tested regardless of their risk of infection, together with making the HIV test readily available to all women, are probably the two best ways of increasing the patients' participation in an HIV-screening program for pregnant women. ^