74 research outputs found

    Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case–control study

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    INTRODUCTION: The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast cancer compared with noncarriers of the mutations, although not all studies have confirmed this association. Haplotype analysis has been suggested as an efficient method for investigating the role of common variation in the ATM gene and breast cancer. Five biallelic haplotype tagging single nucleotide polymorphisms are estimated to capture 99% of the haplotype diversity in Caucasian populations. METHODS: We conducted a nested case–control study of breast cancer within the Nurses' Health Study cohort to address the role of common ATM haplotypes and breast cancer. Cases and controls were genotyped for five haplotype tagging single nucleotide polymorphisms. Haplotypes were predicted for 1309 cases and 1761 controls for which genotype information was available. RESULTS: Six unique haplotypes were predicted in this study, five of which occur at a frequency of 5% or greater. The overall distribution of haplotypes was not significantly different between cases and controls (χ(2 )= 3.43, five degrees of freedom, P = 0.63). CONCLUSION: There was no evidence that common haplotypes of ATM are associated with breast cancer risk. Extensive single nucleotide polymorphism detection using the entire genomic sequence of ATM will be necessary to rule out less common variation in ATM and sporadic breast cancer risk

    Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study

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    BACKGROUND: Mutations in the ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHEK2) genes and amplification of the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene have been suggested to have an important role in breast cancer aetiology. However, whether common variation in these genes has a role in the development of breast cancer or breast cancer survival in humans is still not clear. METHODS: We performed a comprehensive haplotype analysis of the ATM, CHEK2 and ERBB2 genes in a Swedish population-based study, which included 1,579 breast cancer cases and 1,516 controls. We followed the cases for 8.5 years, on average, and retrieved information on the date and cause of death during that period from the nationwide Swedish causes of death registry. We selected seven haplotype-tagging SNPs (tagSNPs) in the ATM gene, six tagSNPs in the CHEK2 gene and seven tagSNPs in the ERBB2 gene that predicted both haplotypic and single locus variations in the respective genes with R(2 )values ≥ 0.8. These tagSNPs were genotyped in the complete set of cases and controls. We computed expected haplotype dosages of the tagSNP haplotypes and included the dosages as explanatory variables in Cox proportional hazards or logistic regression models. RESULTS: We found no association between any genetic variation in the ATM, CHEK2 or ERBB2 genes and breast cancer survival or the risk of developing tumours with certain characteristics. CONCLUSION: Our results indicate that common variants in the ATM, CHEK2 or ERBB2 genes are not involved in modifying breast cancer survival or the risk of tumour-characteristic-defined breast cancer

    The impact of dementia, age and sex on category fluency: Greater deficits in women with Alzheimer's disease

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    Original article can be found at: http://www.sciencedirect.com/science/journal/00109452 Copyright Elsevier Masson DOI: 10.1016/j.cortex.2007.11.008A category specific effect in naming tasks has been reported in patients with Alzheimer's dementia. Nonetheless, naming tasks are frequently affected by methodological problems, e.g., ceiling effects for controls and “nuisance variables” that may confound results. Semantic fluency tasks could help to address some of these methodological difficulties, because they are not prone to producing ceiling effects and are less influenced by nuisance variables. One hundred and thirty-three participants (61 patients with probable AD; and 72 controls: 36 young and 36 elderly) were evaluated with semantic fluency tasks in 14 semantic categories. Category fluency was affected both by dementia and by age: while in nonliving-thing categories there were differences among the three groups, in living thing categories larger lexical categories produced bigger differences among groups. Sex differences in fluency emerged, but these were moderated both by age and by pathology. In particular, fluency was smaller in female than male Alzheimer patients for almost every subcategory.Peer reviewe
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