RESUMO
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.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Estudos de Casos e Controles , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
PURPOSE: Recent work has demonstrated an important decrease in breast cancers for women with systemic lupus erythematosus (SLE). The reason behind this phenomenon is unknown. Our purpose was to explore whether the single nucleotide polymorphisms (SNPs) predisposing to SLE might be protective against breast cancer (in women in the general population). METHODS: We focused on loci relevant to 10 SNPs associated with SLE (with a p value of <10(-9)). We determined whether we could establish a decreased frequency of these SNPs in breast cancer cases versus controls, within the general population. To do this we used a large breast cancer genome-wide association study (GWAS) dataset, involving 3,659 breast cancer cases and 4,897 controls. These subjects were all primarily of European ancestry. RESULTS: The population-based GWAS breast cancer data we examined suggested little evidence for important associations between breast cancer and SLE-related SNPs. Within the general population GWAS data, a cytosine(C) nucleotide substitution at rs9888739 (on chromosome 16p11.2) showed a very weak inverse association with breast cancer. The odds ratio (OR) for the rs9888739-C allele was 0.907551 (p value 0.049899) in the GWAS breast cancer sample, compared to controls. There was a slightly stronger, positive, association with breast cancer for rs6445975-G (Guanine) on chromosome 3p14.3, with a breast cancer OR of 1.0911 (p value 0.0097). CONCLUSIONS: Within this large breast cancer dataset, we did not demonstrate important associations with 10 lupus-associated SNPs. If decreased breast cancer risk in SLE is influenced by genetic profiles, this may be due to complex interactions and/or epigenetic factors.
Assuntos
Neoplasias da Mama/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Alelos , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Razão de Chances , Fatores de Risco , População Branca/genéticaRESUMO
Stereotype threat occurs when individuals, believed to be intellectually inferior, perform badly on cognitive tests they perceive to confirm stereotypes about them. Due to the wide media coverage of studies purporting to show cognitive deficits in ecstasy users it is possible that they experience stereotype threat. This study tested ecstasy and non-ecstasy using polysubstance misusers on a variety of cognitive tests after they had been exposed to stereotype threat. This priming consisted of exposing them to information about the long-term effects of ecstasy which either stated that ecstasy caused memory loss or that it did not. Ecstasy users that had been primed that ecstasy did not cause cognitive deficits performed better than the other three groups on the delayed portion of the prose recall task from the Rivermead Behavioural Memory Test battery. There were no other statistically significant differences between any of the groups on any of the other cognitive tests used. This suggests that stereotype threat exists in ecstasy users and may be influencing their performance in experiments designed to identify cognitive deficits. In order to prevent this occurring in future studies, experimenters must be careful how they conduct their experiments and discuss their results with the media.