FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Glycosylphosphatidylinositol-anchored H-2Db molecules are defective in antigen processing and presentation to cytotoxic T lymphocytes.

Glycosylphosphatidylinositol-anchored (GPI)-Db molecules are defective in mediating cytotoxic T lymphocytes (CTL) lysis of transfected lymphoma cells, compared to their transmembrane (TM) counterpart. This defect is manifest when antigenic peptide must be processed and presented through the endogenous pathway. These same transfectants can be lysed by allospecific CTL, or by antigen-specific Db-restricted CTL when pulsed with appropriate exogenous synthetic peptide, demonstrating that they can bind and present peptide for CTL-mediated lympholysis. The defect apparently results from differences between GPI-Db and TM-Db assembly and transport, or from differences in membrane topology that affect CD8+ CTL recognition of major histocompatibility complex/peptide complex

Interpolating Fields of Carbon Monoxide Data Using a Hybrid Statistical-Physical Model

Atmospheric Carbon Monoxide (CO) is a pollutant gas of which the US congress has mandated regular monitoring, and satellite sensors can be used to retrieve regional concentrations of CO over several vertical layers. However, CO at cloudy locations cannot be observed and have to be estimated from the observed data set, resulting in an interpolation problem. The current state-of-the-art solution is to combine prior information, computed by a deterministic physical model, with observations. However, the deterministic model may introduce uncertainties that do not derive from the data. While sharing certain features with the physical model, this paper presents a Bayesian hierarchical model for interpolating CO on a 3-dimensional spatial grid, across time. To our knowledge such a model has not been considered before. The model is applied to a hypothetical air-quality monitoring scenario, and is compared to existing interpolation methods. The results provide motivation for the use of the statistical model for regional to local applications