Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.

La población infantil de Barcelona (1898-1961): una evaluación de su estado nutricional a partir de estadísticas antropométricas

En los ejercicios de evaluación de la denominada “penalización urbana”, la mortalidad infantil y juvenil suele ser uno o de los indicadores más habituales. Disponer de indicadores relativos a sus condiciones de salud es más difícil. Una opción son los datos antropométricos. Este tipo de información abunda para las poblaciones adultas –especialmente las masculinas enroladas en los ejércitos- pero es más escasa para las infantiles. El propósito de este trabajo es contribuir al conocimiento de las condiciones de salud de este grupo de la población barcelonesa durante algo más de la primera mitad del siglo XX, a partir del estudio de un conjunto de 9 estadísticas antropométricas publicadas entre 1900 y 1961. A través de una reconstrucción estadística, mediante el empleo de las Tablas de Crecimiento de la población infantil española elaboradas por M. Hernández, E Sánchez y B.Sobradillo en 1995, se han estandarizado las tallas y comparado los Indices de Masa Corporal calculados a partir de las medidas publicadas. Los principales resultados son: a) La presencia de diferentes pautas en las trayectorias seculares de crecimiento de niños y niñas. El crecimiento de las tallas entre los niños fue de 1,09 cm por decenio entre 1898 y 1945 y de 1,40 entre 1945 y 1961. Mientras que en el caso de las niñas entre 1898 y 1945 fue de 0,14 cm por decenio para aumentar a 2,18 entre 1945 y 1981. b) Las diferencias sociales en los indicadores antropométricos persisten a lo largo del periodo estudiado c) Los porcentajes de población infantil con probable malnutrición se situaron en torno al 24 por ciento para las generaciones nacidas entre 1885 y 1940, para ir descendiendo de forma irreversible en las nacidas a partir de 1950. De este modo en la década años setenta del siglo XX no parece existir evidencia de tal estado en la población infantil barcelonesa.

Peutz-Jeghers syndrome: a systematic review and recommendations for management

Peutz¿Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype¿phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.