A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.
paper
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- Authors
- Hunter, David J; Kraft, Peter; Jacobs, Kevin B; Cox, David G; Yeager, Meredith; Hankinson, Susan E; Wacholder, Sholom; Wang, Zhaoming; Welch, Robert; Hutchinson, Amy; Wang, Junwen; Yu, Kai; Chatterjee, Nilanjan; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F; Hoover, Robert N; Thomas, Gilles; Chanock, Stephen J
- Year
- 2007
- Journal
- Nature genetics
- PMID
- 17529973
- DOI
- 10.1038/ng2075
- PMCID
- PMC3493132
We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.
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| Genetic association analysis of copy-number variation (CNV) in human disease pathogenesis. | Ionita-Laza I et al. | β | 2009 | β |
| Genetic background comparison using distance-based regression, with applications in population stratification evaluation and adjustment. | Li Q et al. | β | 2009 | β |
| Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk. | Reding KW et al. | β | 2009 | β |
| Genetic prognostic and predictive markers in colorectal cancer. | Walther A et al. | β | 2009 | β |
| Genetics and personal genomics for personalized breast cancer surgery: progress and challenges in research and clinical practice. | Ziogas D et al. | β | 2009 | β |
| Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study. | Nan H et al. | β | 2009 | β |
| Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. | Nan H et al. | β | 2009 | β |
| Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis. | Gaudet MM et al. | β | 2009 | β |
| Genetic variation in the chromosome 17q23 amplicon and breast cancer risk. | Kelemen LE et al. | β | 2009 | β |
| Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk. | Chen M et al. | β | 2009 | β |
| Genome-wide and candidate gene association study of cigarette smoking behaviors. | Caporaso N et al. | β | 2009 | β |
| Genome-wide association analyses identify SPOCK as a key novel gene underlying age at menarche. | Liu YZ et al. | β | 2009 | β |
| Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15. | Liu YZ et al. | β | 2009 | β |
| Genome-wide association scans for secondary traits using case-control samples. | Monsees GM et al. | β | 2009 | β |
| Genome-wide association studies and the genetic dissection of complex traits. | Sebastiani P et al. | β | 2009 | β |
| Genome-wide association studies: how predictable is a person's cancer risk? | Roukos DH | β | 2009 | β |
| Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. | He C et al. | β | 2009 | β |
| Genome-wide association studies of bladder cancer risk: a field synopsis of progress and potential applications. | Wu X et al. | β | 2009 | β |
| Genome-wide association studies of coronary artery disease and heart failure: where are we going? | Dorn GW et al. | β | 2009 | β |
| Genome-wide association study for type 2 diabetes: clinical applications. | Lyssenko V et al. | β | 2009 | β |
| Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. | Zheng W et al. | β | 2009 | β |
| Genome-wide association study identifies five susceptibility loci for glioma. | Shete S et al. | β | 2009 | β |
| Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. | Amundadottir L et al. | β | 2009 | β |
| Genome-wide association study of tanning phenotype in a population of European ancestry. | Nan H et al. | β | 2009 | β |
| Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility. | Knight JA et al. | β | 2009 | β |
| Genome-wide profiling of chromosomal alterations in renal cell carcinoma using high-density single nucleotide polymorphism arrays. | Chen M et al. | β | 2009 | β |
| Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. | Hazra A et al. | β | 2009 | β |
| GRM7 variants confer susceptibility to age-related hearing impairment. | Friedman RA et al. | β | 2009 | β |
| Heritable variation of ERBB2 and breast cancer risk. | Breyer JP et al. | β | 2009 | β |
| High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays. | Wang J et al. | β | 2009 | β |
| Histone-acetylated control of fibroblast growth factor receptor 2 intron 2 polymorphisms and isoform splicing in breast cancer. | Zhu X et al. | β | 2009 | β |
| Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women. | Rebbeck TR et al. | β | 2009 | β |
| Human genetic variations: Beacons on the pathways to successful ageing. | Cluett C et al. | β | 2009 | β |
| Identification of Novel Susceptibility Genes for Breast Cancer - Genome-Wide Association Studies or Evaluation of Candidate Genes? | Meindl A | β | 2009 | β |
| Insulin-like growth factor-1- and interleukin-6-related gene variation and risk of multiple myeloma. | Birmann BM et al. | β | 2009 | β |
| Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power. | Becker T et al. | β | 2009 | β |
| Low penetrance breast cancer predisposition SNPs are site specific. | Mcinerney N et al. | β | 2009 | β |
| Low-risk susceptibility alleles in 40 human breast cancer cell lines. | Riaz M et al. | β | 2009 | β |
| Mammary tumor development in dogs is associated with BRCA1 and BRCA2. | Rivera P et al. | β | 2009 | β |
| Methods for analysis in pharmacogenomics: lessons from the Pharmacogenetics Research Network Analysis Group. | Srinivasan BS et al. | β | 2009 | β |
| Microarray methods to identify factors determining breast cancer progression: potentials, limitations, and challenges. | van der Vegt B et al. | β | 2009 | β |
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| Mucinous and neuroendocrine breast carcinomas are transcriptionally distinct from invasive ductal carcinomas of no special type. | Weigelt B et al. | β | 2009 | β |
| Needles in the haystack: identifying individuals present in pooled genomic data. | Braun R et al. | β | 2009 | β |
| Negative regulation of fibroblast growth factor 10 (FGF-10) by polyoma enhancer activator 3 (PEA3). | Chioni AM et al. | β | 2009 | β |
| Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. | Ahmed S et al. | β | 2009 | β |
| No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. | Teras LR et al. | β | 2009 | β |
| Nonmetric multidimensional scaling corrects for population structure in association mapping with different sample types. | Zhu C et al. | β | 2009 | β |
| On quality control measures in genome-wide association studies: a test to assess the genotyping quality of individual probands in family-based association studies and an application to the HapMap data. | Fardo DW et al. | β | 2009 | β |
| p53 polymorphisms: cancer implications. | Whibley C et al. | β | 2009 | β |
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| Polygenic susceptibility to breast cancer: current state-of-the-art. | Ghoussaini M et al. | β | 2009 | β |
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| Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994. | Chang MH et al. | β | 2009 | β |
| Recovering unused information in genome-wide association studies: the benefit of analyzing SNPs out of Hardy-Weinberg equilibrium. | Fardo DW et al. | β | 2009 | β |
| Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. | Milne RL et al. | β | 2009 | β |
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| Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort. | Haiman CA et al. | β | 2009 | β |
| SNP-SNP interactions between dNTP supply enzymes and mismatch DNA repair in breast cancer. | Feng IJ et al. | β | 2009 | β |
| Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement. | Little J et al. | β | 2009 | β |
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| Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement. | Little J et al. | β | 2009 | β |
| STrengthening the REporting of Genetic Association studies (STREGA)--an extension of the STROBE statement. | Little J et al. | β | 2009 | β |
| STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE Statement. | Little J et al. | β | 2009 | β |
| STrengthening the REporting of Genetic Association Studies (STREGA)--an extension of the STROBE statement. | Little J et al. | β | 2009 | β |
| STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement. | Little J et al. | β | 2009 | β |
| Studying genetic variations in cancer prognosis (and risk): a primer for clinicians. | Savas S et al. | β | 2009 | β |
| The 6q22.33 locus and breast cancer susceptibility. | Kirchhoff T et al. | β | 2009 | β |
| The contribution of BRCA1 and BRCA2 to ovarian cancer. | Ramus SJ et al. | β | 2009 | β |
| The medical and economic roles of pipeline pharmacogenetics: Alzheimer's disease as a model of efficacy and HLA-B(*)5701 as a model of safety. | Roses AD | β | 2009 | β |
| The mitochondrial A10398G polymorphism, interaction with alcohol consumption, and breast cancer risk. | Pezzotti A et al. | β | 2009 | β |
| The null distributions of test statistics in genomewide association studies. | Chen X et al. | β | 2009 | β |
| The RNF146 and ECHDC1 genes as candidates for inherited breast and ovarian cancer in Jewish Ashkenazi women. | Menachem TD et al. | β | 2009 | β |
| The role of senescence and prosurvival signaling in controlling the oncogenic activity of FGFR2 mutants associated with cancer and birth defects. | Ota S et al. | β | 2009 | β |
| Update on genetic predisposition to breast cancer. | Ahmed M et al. | β | 2009 | β |
| Using lifetime risk estimates in personal genomic profiles: estimation of uncertainty. | Yang Q et al. | β | 2009 | β |
| Using prior knowledge and genome-wide association to identify pathways involved in multiple sclerosis. | Ritchie MD | β | 2009 | β |
| Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer. | Prentice RL et al. | β | 2009 | β |
| Visualization of shared genomic regions and meiotic recombination in high-density SNP data. | Roberson ED et al. | β | 2009 | β |
| Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer. | McCullough ML et al. | β | 2009 | β |
| Willows: a memory efficient tree and forest construction package. | Zhang H et al. | β | 2009 | β |
| Zebrafish Hagoromo mutants up-regulate fgf8 postembryonically and develop neuroblastoma. | Amsterdam A et al. | β | 2009 | β |
| Advances in breast cancer: pathways to personalized medicine. | Olopade OI et al. | β | 2008 | β |
| A range of cancers is associated with the rs6983267 marker on chromosome 8. | Wokolorczyk D et al. | β | 2008 | β |
| Association of common PALB2 polymorphisms with breast cancer risk: a case-control study. | Chen P et al. | β | 2008 | β |
| Association studies of common variants in 10 hypogonadotropic hypogonadism genes with age at menarche. | Gajdos ZK et al. | β | 2008 | β |
| Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes. | Bonifaci N et al. | β | 2008 | β |
| Cancer genetic association studies in the genome-wide age. | Savage SA | β | 2008 | β |
| Can genes for mammographic density inform cancer aetiology? | Kelemen LE et al. | β | 2008 | β |
| Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis. | Giulianelli S et al. | β | 2008 | β |
| Common variants of FUT2 are associated with plasma vitamin B12 levels. | Hazra A et al. | β | 2008 | β |
| Discovering interactions among BRCA1 and other candidate genes associated with sporadic breast cancer. | Lo SH et al. | β | 2008 | β |
| Expectations and challenges stemming from genome-wide association studies. | Vineis P et al. | β | 2008 | β |
| Genetic mapping of mammary tumor traits to rat chromosome 10 using a novel panel of consomic rats. | Adamovic T et al. | β | 2008 | β |
| Genetics and genome-wide association studies: surgery-guided algorithm and promise for future breast cancer personalized surgery. | Roukos DH | β | 2008 | β |
| Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. | Buysschaert I et al. | β | 2008 | β |
| Genetic susceptibility loci for breast cancer by estrogen receptor status. | Garcia-Closas M et al. | β | 2008 | β |
| Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women. | Liang J et al. | β | 2008 | β |
| Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies. | Kelemen LE et al. | β | 2008 | β |
| Genome-wide association studies in cancer. | Easton DF et al. | β | 2008 | β |
| Genomic predictors of interindividual differences in response to DNA damaging agents. | Fry RC et al. | β | 2008 | β |
| Genomics and challenges toward personalized breast cancer local control. | Roukos DH et al. | β | 2008 | β |
| Identification of alternative splicing markers for breast cancer. | Venables JP et al. | β | 2008 | β |
| Identification of low penetrance alleles for lung cancer: the GEnetic Lung CAncer Predisposition Study (GELCAPS). | Eisen T et al. | β | 2008 | β |
| Identification of personal risk of breast cancer: genetics. | Eccles DM | β | 2008 | β |
| Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study. | Liu YZ et al. | β | 2008 | β |
| Inherited susceptibility to common cancers. | Foulkes WD | β | 2008 | β |
| Major trends in the imaging sciences: 2007 Eugene P. Pendergrass New Horizons Lecture. | Zerhouni EA | β | 2008 | β |
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| New cancer susceptibility loci: population and familial risks. | Hemminki K et al. | β | 2008 | β |
| Novel breast cancer risk alleles and endometrial cancer risk. | McGrath M et al. | β | 2008 | β |
| Obesity genes and gene-environment-behavior interactions: recommendations for a way forward. | Shuldiner AR | β | 2008 | β |
| Pharmacogenetics in drug discovery and development: a translational perspective. | Roses AD | β | 2008 | β |
| Quantitative analysis of single nucleotide polymorphisms within copy number variation. | Lee S et al. | β | 2008 | β |
| Role of TGF-beta and FGF in the treatment of radiation-impaired wounds using a novel drug delivery system. | Tattini C et al. | β | 2008 | β |
| Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. | Plon SE et al. | β | 2008 | β |
| Social and ethical implications of genomics, race, ethnicity, and health inequities. | Bonham VL et al. | β | 2008 | β |
| The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. | Liu W et al. | β | 2008 | β |
| Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance. | Hofstra RM et al. | β | 2008 | β |
| Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population. | Sinotte M et al. | β | 2008 | β |