Single Nucleotide Polymorphisms in the Wnt and BMP Pathways and Colorectal Cancer Risk in a Spanish Cohort

BACKGROUND: Colorectal cancer (CRC) is considered a complex disease, and thus the majority of the genetic susceptibility is thought to lie in the form of low-penetrance variants following a polygenic model of inheritance. Candidate-gene studies have so far been one of the basic approaches taken to identify these susceptibility variants. The consistent involvement of some signaling routes in carcinogenesis provided support for pathway-based studies as a natural strategy to select genes that could potentially harbour new susceptibility loci. METHODOLOGY/PRINCIPAL FINDINGS: We selected two main carcinogenesis-related pathways: Wnt and BMP, in order to screen the implicated genes for new risk variants. We then conducted a case-control association study in 933 CRC cases and 969 controls based on coding and regulatory SNPs. We also included rs4444235 and rs9929218, which did not fulfill our selection criteria but belonged to two genes in the BMP pathway and had consistently been linked to CRC in previous studies. Neither allelic, nor genotypic or haplotypic analyses showed any signs of association between the 37 screened variants and CRC risk. Adjustments for sex and age, and stratified analysis between sporadic and control groups did not yield any positive results either. CONCLUSIONS/SIGNIFICANCE: Despite the relevance of both pathways in the pathogenesis of the disease, and the fact that this is indeed the first study that considers these pathways as a candidate-gene selection approach, our study does not present any evidence of the presence of low-penetrance variants for the selected markers in any of the considered genes in our cohort

The revised Bethesda guidelines: extent of utilization in a university hospital medical center with a cancer genetics program

<p>Abstract</p> <p>Background</p> <p>In 1996, the National Cancer Institute hosted an international workshop to develop criteria to identify patients with colorectal cancer who should be offered microsatellite instability (MSI) testing due to an increased risk for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). These criteria were further modified in 2004 and became known as the revised Bethesda Guidelines. Our study aimed to retrospectively evaluate the percentage of patients diagnosed with HNPCC tumors in 2004 who met revised Bethesda criteria for MSI testing, who were referred for genetic counseling within our institution.</p> <p>Methods</p> <p>All HNPCC tumors diagnosed in 2004 were identified by accessing CoPath, an internal database. Both the Tumor Registry and patients' electronic medical records were accessed to collect all relevant family history information. The list of patients who met at least one of the revised Bethesda criteria, who were candidates for MSI testing, was then cross-referenced with the database of patients referred for genetic counseling within our institution.</p> <p>Results</p> <p>A total of 380 HNPCC-associated tumors were diagnosed at our institution during 2004 of which 41 (10.7%) met at least one of the revised Bethesda criteria. Eight (19.5%) of these patients were referred for cancer genetic counseling of which 2 (25%) were seen by a genetics professional. Ultimately, only 4.9% of patients eligible for MSI testing in 2004 were seen for genetic counseling.</p> <p>Conclusion</p> <p>This retrospective study identified a number of barriers, both internal and external, which hindered the identification of individuals with HNPCC, thus limiting the ability to appropriately manage these high risk families.</p

Are women and providers satisfied with antenatal care? Views on a standard and a simplified, evidence-based model of care in four developing countries

BACKGROUND: This study assessed women and providers' satisfaction with a new evidence-based antenatal care (ANC) model within the WHO randomized trial conducted in four developing countries. The WHO study was a randomized controlled trial that compared a new ANC model with the standard type offered in each country. The new model of ANC emphasized actions known to be effective in improving maternal or neonatal health, excluded other interventions that have not proved to be beneficial, and improved the information component, especially alerting pregnant women to potential health problems and instructing them on appropriate responses. These activities were distributed within four antenatal care visits for women that did not need any further assessment. METHODS: Satisfaction was measured through a standardized questionnaire administered to a random sample of 1,600 pregnant women and another to all antenatal care providers. RESULTS: Most women in both arms expressed satisfaction with ANC. More women in the intervention arm were satisfied with information on labor, delivery, family planning, pregnancy complications and emergency procedures. More providers in the experimental clinics were worried about visit spacing, but more satisfied with the time spent and information provided. CONCLUSIONS: Women and providers accepted the new ANC model generally. The safety of fewer visits for women without complications with longer spacing would have to be reinforced, if such a model is to be introduced into routine practice