association between common variation in 120 candidate genes and breast cancer risk常见变异之间的关系在120年候选基因和乳腺癌的风险.pdf

Association between Common Variation in 120 Candidate Genes and Breast Cancer Risk 1,2* 1 1 2 1 Paul D. P. Pharoah , Jonathan Tyrer , Alison M. Dunning , Douglas F. Easton , Bruce A. J. Ponder , SEARCH Investigators 1 Department of Oncology, University of Cambridge, Cambridge, United Kingdom, 2 Strangeways Research Laboratory, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom Association studies in candidate genes have been widely used to search for common low penetrance susceptibility alleles, but few definite associations have been established. We have conducted association studies in breast cancer using an empirical single nucleotide polymorphism (SNP) tagging approach to capture common genetic variation in genes that are candidates for breast cancer based on their known function. We genotyped 710 SNPs in 120 candidate genes in up to 4,400 breast cancer cases and 4,400 controls using a staged design. Correction for population stratification was done using the genomic control method, on the basis of data from 280 genomic control SNPs. Evidence for association with each SNP was assessed using a Cochran–Armitage trend test (p-trend) and a two-degrees of freedom v2 test for heterogeneity (p-het). The most significant single SNP (p-trend ¼ 8 3 105) was not significant at a nominal 5% level after adjusting for population stratification and multiple testing. To evaluate the overall evidence for an excess of positive associations over the proportion expected by chance, we applied two global tests: the admixture maximum likelihood (AML) test and the rank truncated product (RTP) test corrected for population stratification. The admixture maximum