Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult.</p> <p>Methods</p> <p>A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined.</p> <p>Results</p> <p>Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2) had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65).</p> <p>Conclusion</p> <p>A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations.</p

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Nodal signalling is involved in left-right asymmetry in snails

5 pages, 4 figures.-- Supplementary information (figures 1-5, tables 1-3, supplementary methods and supplementary results) available at the publisher's site: http://www.nature.com/nature/journal/vaop/ncurrent/suppinfo/nature07603.html.Nodal, Pitx and hedgehog sequences of L. gigantea and B. glabrata are deposited at the EMBL-GenBank data libraries; accession numbers EU394708 and EU394707 (for nodal), EU797117 and EU797116 (for Pitx) and EU394706 and EU394705 (for hedgehog). In addition, a brachyury sequence of L. gigantea is deposited as accession number EU797118.Many animals display specific internal or external features with left–right asymmetry. In vertebrates, the molecular pathway that leads to this asymmetry uses the signalling molecule Nodal, a member of the transforming growth factor-β superfamily, which is expressed in the left lateral plate mesoderm, and loss of nodal function produces a randomization of the left–right asymmetry of visceral organs. Orthologues of nodal have also been described in other deuterostomes, including ascidians and sea urchins, but no nodal orthologue has been reported in the other two main clades of Bilateria: Ecdysozoa (including flies and nematodes) and Lophotrochozoa (including snails and annelids). Here we report the first evidence for a nodal orthologue in a non-deuterostome group. We isolated nodal and Pitx (one of the targets of Nodal signalling) in two species of snails and found that the side of the embryo that expresses nodal and Pitx is related to body chirality: both genes are expressed on the right side of the embryo in the dextral (right-handed) species Lottia gigantea and on the left side in the sinistral (left-handed) species Biomphalaria glabrata. We pharmacologically inhibited the Nodal pathway and found that nodal acts upstream of Pitx, and that some treated animals developed with a loss of shell chirality. These results indicate that the involvement of the Nodal pathway in left–right asymmetry might have been an ancestral feature of the Bilateria.C.G. was sponsored by a postdoctoral fellowship of the Ministerio de Educación y Ciencia (Spain) and the Center for Integrative Genomics. N.H.P. is an Investigator of the Howard Hughes Medical Institute.Peer reviewe