Abstract
Familial clustering studies indicate that breast cancer risk has a substantial genetic component1,2,3. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: ∼25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor–positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5′ end of TNRC9 , a high mobility group chromatin–associated protein whose expression is implicated in breast cancer metastasis to bone4.
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Acknowledgements
We thank all participants for taking part in this research. We thank S. Sveinsdottir and K. Alexiusdottir for assistance in recruitment of patients and collection of clinical information. This project was funded in part by contract number 018827 (POLYGENE) from the 6th Framework Program of the European Union, the Swedish Cancer Society, the Gustav V Jubilee Foundation, the Bert von Kantzow Foundation and the Nilsson-Ehle Foundation.
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Simon N Stacey, Andrei Manolescu, Patrick Sulem, Thorunn Rafnar, Julius Gudmundsson, Sigurjon A Gudjonsson, Gisli Masson, Margret Jakobsdottir, Steinunn Thorlacius, Agnar Helgason, Magali Mouy, Jona Saemundsdottir, Valgerdur M Backman, Larus Gudmundsson, Kristleifur Kristjansson, Jon T Bergthorsson, Jelena Kostic, Michael L Frigge, Frank Geller, Daniel Gudbjartsson, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong and Kari Stefansson are employees and/or shareholders of deCODE genetics.
Supplementary information
Supplementary Fig. 1
Q-Q plot for 311,524 SNPs. (PDF 156 kb)
Supplementary Table 1
Association results for SNPs that did not replicate significantly outside Iceland. (PDF 43 kb)
Supplementary Table 2
Comparison of recently diagnosed and long-term survivor groups of Icelandic breast cancer patients. (PDF 52 kb)
Supplementary Table 3
Swedish Familial and consecutively recruited breast cancer patient groups. (PDF 38 kb)
Supplementary Table 4
Odds ratios for A-rs13387042 and T-rs3803662 in carriers and noncarriers of the Icelandic BRCA2 999del5 mutation. (PDF 58 kb)
Supplementary Table 5
Primers used in Centaurus SNP and PCR assays. (PDF 65 kb)
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Stacey, S., Manolescu, A., Sulem, P. et al. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer. Nat Genet 39, 865–869 (2007). https://doi.org/10.1038/ng2064
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DOI: https://doi.org/10.1038/ng2064
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