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Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1


We carried out a genome-wide association study among Chinese women to identify risk variants for breast cancer. After analyzing 607,728 SNPs in 1,505 cases and 1,522 controls, we selected 29 SNPs for a fast-track replication in an independent set of 1,554 cases and 1,576 controls. We further investigated four replicated loci in a third set of samples comprising 3,472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the gene encoding estrogen receptor α (ESR1), showed strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24–1.49) and 1.59 (1.40–1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend 2.0 × 10−15) in the pooled analysis of samples from all three stages. We also found a similar, albeit weaker, association in an independent study comprising 1,591 cases and 1,466 controls of European ancestry (Ptrend = 0.01). These results strongly implicate 6q25.1 as a susceptibility locus for breast cancer.

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Figure 1: Genome-wide association results in the Shanghai Breast Cancer Study.
Figure 2: Regional plot of the chromosome 6q25.1 locus.


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This research was supported in part by US National Institutes of Health grants R01CA124558, R01CA64277, R01CA70867, R01CA90899 and R01CA100374, as well as Ingram professorship funds and research award funds to W.Z., R01 CA118229, R01CA92585 and Department of Defense (DOD) Idea Award BC011118 to X.-O.S., and R01CA122756 and DOD Idea Award BC050791 to Q.C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors wish to thank study participants and research staff for their contributions and commitment to this project, R. Courtney and Q. Wang for DNA preparation, and B. Venuti for clerical support in the preparation of this manuscript. Sample preparation and stage 1 genotyping were conducted at the Survey and Biospecimen and Microarray Shared Resources that are supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). Stage 2 and 3 genotyping was carried out at the Proactive Genomics.

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Authors and Affiliations



W.Z. directed the study and drafted the manuscript along with J.L., Q.C. and X.-O.S. J.L. coordinated the study and managed the genotyping data. Q.C. directed the lab operation. J.L., C.L. and W.W. performed statistical analyses. W.Z. directed the SBCS and the NBHS, and X.-O.S. directed the SBCSS and the SECS, the four parent studies. Y.-T.G., Y.-B.X. and W.L. directed the data and sample collection of SBCS, SBCSS and SECS in Shanghai. Y.Z. and K.G. supervised data and sample collection. S.L.D. and A.M.F. coordinated the NBHS. S.L. directed stage 1 genotyping. C.L., S.L. and J.L.H. contributed to manuscript revision. All authors reviewed and approved the final manuscript.

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Correspondence to Wei Zheng.

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Zheng, W., Long, J., Gao, YT. et al. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41, 324–328 (2009).

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