Showing papers by "Nichola Johnson published in 2007"
University of Cambridge1, National Institutes of Health2, University of Southern California3, International Agency for Research on Cancer4, Academia Sinica5, Princess Anne Hospital6, St Mary's Hospital7, University of London8, The Breast Cancer Research Foundation9, Wellcome Trust Sanger Institute10, Peter MacCallum Cancer Centre11, QIMR Berghofer Medical Research Institute12, University of Copenhagen13, Curie Institute14, Nofer Institute of Occupational Medicine15, University of Helsinki16, Seoul National University17, University of Ulsan18, Harvard University19, Karolinska Institutet20, Agency for Science, Technology and Research21, Hannover Medical School22, Leiden University23, Erasmus University Rotterdam24, University of Minnesota25, University of Sheffield26, Mayo Clinic27, VU University Amsterdam28, Carlos III Health Institute29, University of Melbourne30, University of Otago31, Cancer Council New South Wales32, Cancer Council Victoria33, University of Tübingen34, Bosch35, German Cancer Research Center36, University of Eastern Finland37
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
2,288 citations
TL;DR: Investigating the effect of TP53 R72P and MDM2 SNP309 on breast cancer risk and age at onset of breast cancer in a pooled series of 5,191 cases and 3,834 controls found no association with breast cancer.
Abstract: Association studies in large series of breast cancer patients can be used to identify single-nucleotide polymorphisms (SNP) contributing to breast cancer susceptibility. Previous studies have suggested associations between variants in TP53 (R72P) and MDM2 (SNP309) and cancer risk. Data from molecular studies suggest a functional interaction between these genes. We therefore investigated the effect of TP53 R72P and MDM2 SNP309 on breast cancer risk and age at onset of breast cancer in a pooled series of 5,191 cases and 3,834 controls from the Breast Cancer Association Consortium (BCAC). Breast cancer risk was not found to be associated with the combined variant alleles [odds ratio (OR), 1.00; 95% confidence interval (95% CI), 0.81-1.23]. Estimated ORs were 1.01 (95% CI, 0.93-1.09) per MDM2 SNP309 allele and 0.98 (95% CI, 0.91-1.04) for TP53 R72P. Although we did find evidence for a 4-year earlier age at onset for carriers of both variant alleles in one of the breast cancer patient series of the BCAC (the German series), we were not able to confirm this effect in the pooled analysis. Even so, carriers of both variant alleles did not have different risk estimates for bilateral or estrogen receptor-positive breast cancer. In conclusion, in this large collaborative study, we did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer. This suggests that any effect of these two variants would be very small and possibly confined to subgroups that were not assessed in our present study.
81 citations
TL;DR: In the version of this article initially published, there was an error that affected the calculations of the odds ratios, confidence intervals, between-study heterogeneity, trend test and test for association for SNP ICAM5 V301I as discussed by the authors.
Abstract: Nat. Genet. 39, 352–358 (2007); published online 11 February 2007; corrected 10 April 2007 In the version of this article initially published, there was an error that affected the calculations of the odds ratios, confidence intervals, between-study heterogeneity, trend test and test for association for SNP ICAM5 V301I in Table 1 (ICAM5 V301I); genotype counts in Supplementary Table 2 (ICAM5; ICR_FBCS and Kuopio studies) and minor allele frequencies, trend test and odds ratios for heterozygotes and rare homozygotes in Supplementary Table 3 (ICAM5; ICR_FBCS and Kuopio studies).
5 citations