The general public's information needs and perceptions regarding hereditary cancer: an application of the Integrated Change Model

The Integrated Change Model (the I-Change Model) was used to analyse the general public's need and perceptions concerning receiving information on the role of hereditary factors with regard to cancer. The results from a study in 457 Dutch adults showed that 25% correctly indicated the types of cancer where hereditary factors can play a role. Respondents, however, overestimated the role of hereditary factors causing breast cancer. Recognition of warning signs was low, as was the recognition of inheritance patterns. Participants wanted to know the types of cancer with hereditary aspects, how to recognise hereditary cancer in the family, personal risks and the steps to be taken when hereditary predisposition is suspected. The most popular information channels mentioned were leaflets, the general practitioner, and the Internet. Respondents interested in receiving information on heredity and cancer were more often female, had had experiences with hereditary diseases, had more knowledge, perceived more advantages, encountered more social support in seeking information, and had higher levels of self-efficacy. Education should outline the most important facts about hereditary cancer, how to get support, and create realistic expectations of the impact of genetic factors.     

A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia

Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of leukemic blasts. This concept represented the rationale for the initiation of a multicenter phase 2 trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor, and fms-like tyrosine kinase-3 (FLT3) in patients with advanced AML. Entered into the study were 43 patients with refractory AML or elderly patients not judged medically fit for intensive induction chemotherapy; 42 patients received at least one dose of study drug. Treatment was generally well tolerated, with nausea, headache, and bone pain the most frequent treatment-related side effects. One patient had a morphologic remission (French-American-British [FAB] criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. There were 7 patients who achieved a partial response (reduction of blasts by at least 50% in bone marrow and peripheral blood) lasting 1 to 5 months. Patients with AML blasts expressing high levels of VEGF mRNA by quantitative polymerase chain reaction (PCR) had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the antiangiogenic effects of SU5416.     

Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study

Screening for inherited thrombophilia (IT) is controversial; persons at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first- and second-degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. The risk for VTE was significantly increased among family members with, versus without, IT (hazard ratio = 7.6; 95% confidence interval [CI], 4.0-14.5; P < .001) and highest among carriers of antithrombin, protein C, or protein S deficiency (hazard ratio = 25.7; 95% CI, 12.2-54.2; P < .001). Annual incidences of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S, and antithrombin deficiency, we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess whether thromboembolism can be prevented in this high-risk population.