Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer
Abstract
Familial clustering studies indicate that breast cancer risk has a substantial genetic component. 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: approximately 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 bone.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent genome-wide association studies have detected SNPs significantly associated with breast cancer, colorectal cancer, type 2 diabetes, and heart disease, among other diseases.
“This idea, combined with the development of efficient methods for surveying large numbers of SNPs, has led to the many recent genome-wide association (GWA) studies that have detected SNPs that are significantly associated with breast cancer79,80, colorectal cancer81,82, type 2 diabetes83–86 and heart disease87,88, among other diseases.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [80]
Cites
Lichtenstein, P., Holm, N. V., Verkasalo, P. K., Iliadou, A., Kaprio, J., Koskenvuo, M., Pukkala, E., Skytthe, A., & Hemminki, K. (2000) · New England Journal of Medicine · doi:10.1056/nejm200007133430201 · Cited by 4,114 · see citing works
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · see citing works
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Grant, S. F. A., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., et al. (2006) · Nature Genetics · doi:10.1038/ng1732 · Cited by 2,287 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Genome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891 · see citing works
Linkage disequilibrium--understanding the evolutionary past and mapping the medical future.
Slatkin, M. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2361 · Cited by 1,614 · see citing works
Replicating genotype–phenotype associations
NCI-NHGRI Working Group on Replication in Association Studies, Chanock, S. J., Manolio, T., Boehnke, M., Boerwinkle, E., Hunter, D. J., Thomas, G., Hirschhorn, J. N., Abecasis, G., Altshuler, D., et al. (2007) · Nature · doi:10.1038/447655a · Cited by 1,352 · see citing works
(2012) · The Lancet · doi:10.1016/s0140-6736(12)60110-x · Cited by 1,146 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
Little, J., Higgins, J. P. T., Ioannidis, J. P. A., Moher, D., Gagnon, F., von Elm, E., Khoury, M. J., Cohen, B., Davey-Smith, G., Grimshaw, J., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000022 · Cited by 811 · see citing works
Genome-wide association study identifies five new breast cancer susceptibility loci
The Breast Cancer Susceptibility Collaboration (UK), Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.586 · Cited by 687 · see citing works
The emerging landscape of breast cancer susceptibility
Stratton, M. R., & Rahman, N. (2008) · Nature Genetics · doi:10.1038/ng.2007.53 · Cited by 487 · see citing works
Panagiotou, O. A., Ioannidis, J. P. A., & for the Genome-Wide Significance Project (2012) · International Journal of Epidemiology · doi:10.1093/ije/dyr178 · Cited by 286 · see citing works
Sætrom, P., Biesinger, J., Li, S. M., Smith, D., Thomas, L. F., Majzoub, K., Rivas, G. E., Alluin, J., Rossi, J. J., Krontiris, T. G., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1201 · Cited by 138 · see citing works
Cai, Q., Wen, W., Qu, S., Li, G., Egan, K. M., Chen, K., Deming, S. L., Shen, H., Shen, C.-Y., Gammon, M. D., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2733 · Cited by 85 · see citing works
Self-citationGenome-wide association studies and the genetic dissection of complex traits
Sebastiani, P., Timofeev, N., Dworkis, D. A., Perls, T. T., & Steinberg, M. H. (2009) · American Journal of Hematology · doi:10.1002/ajh.21440 · Cited by 67 · see citing works
- Authors
- Stacey, S. N., Manolescu, A., Sulem, P., Rafnar, T., Gudmundsson, J., Gudjonsson, S. A., Masson, G., Jakobsdottir, M., Thorlacius, S., Helgason, A., Aben, K. K., Strobbe, L. J., Albers-Akkers, M. T., Swinkels, D. W., Henderson, B. E., Kolonel, L. N., Le Marchand, L., Millastre, E., Andres, R., Godino, J., Garcia-Prats, M. D., Polo, E., Tres, A., Mouy, M., Saemundsdottir, J., Backman, V. M., Gudmundsson, L., Kristjansson, K., Bergthorsson, J. T., Kostic, J., Frigge, M. L., Geller, F., Gudbjartsson, D., Sigurdsson, H., Jonsdottir, T., Hrafnkelsson, J., Johannsson, J., Sveinsson, T., Myrdal, G., Grimsson, H. N., Jonsson, T., von Holst, S., Werelius, B., Margolin, S., Lindblom, A., Mayordomo, J. I., Haiman, C. A., Kiemeney, L. A., Johannsson, O. T., Gulcher, J. R., Thorsteinsdottir, U., Kong, A., & Stefansson, K.
- Affiliations
- deCODE Genetics (Iceland) (IS)
- Radboud University Nijmegen (NL)
- Canisius-Wilhelmina Ziekenhuis (NL)
- University of Southern California (US)
- University of Hawaiʻi at Mānoa (US)
- National University Hospital of Iceland (IS)
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Stacey, Simon N
- ORCID
- Stacey, Simon N
- Manolescu, Andrei
- Sulem, Patrick
- Gudjonsson, Sigurjon A
- Helgason, Agnar
- Aben, Katja K
- Strobbe, Luc J
- Swinkels, Dorine W
- Kolonel, Laurence N
- Kostic, Jelena
- Frigge, Michael L
- Geller, Frank
- Gudbjartsson, Daniel
- Margolin, Sara
- Lindblom, Annika
- Mayordomo, Jose I
- Haiman, Christopher A
- Kiemeney, Lambertus A
- Kong, Augustine
- Venue
- Nature Genetics
- Published
- 2007-05-27
- Volume
- 39
- Issue
- 7
- Pages
- 865-869
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2031772624
- Cited by
- 786
- References
- 3
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 15 · 2019: 19 · 2018: 25 · 2017: 21 · 2016: 40 · 2015: 37 · 2014: 48 · 2013: 65 · 2012: 70
- FWCI
- 57.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- European Commission
- Radboud Universiteit
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- estrogen receptor-positive breast cancer, genetic susceptibility, chromosome 2q35, single nucleotide polymorphisms, bone metastasis, Icelandic population, linkage disequilibrium
- MeSH terms
- Breast Neoplasms, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 2, Female, Humans, Receptors, Estrogen, Genetic Variation, Case-Control Studies, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
