title: Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.
abstract: BACKGROUND
  Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles.
  
  
  METHODS
  We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs.
  
  
  RESULTS
  Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts.
  
  
  CONCLUSIONS
  This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.
authors.affiliation: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, Baldinca Li Punti, 07100, Sassari, Italy. graziap68@yahoo.it.
authors.forename: Grazia
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authors.lastname: Palomba
authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. loiangela@hotmail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Loi
authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. eleonoraporcu@gmail.com.
authors.forename: Eleonora
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authors.lastname: Porcu
authors.affiliation: Istituto di Anatomia Patologica, Azienda Ospedaliero Universitaria, Sassari, Italy. cossu@uniss.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Center for Advanced Studies, Research and Development in Sardina (CRS4), Pula, Cagliari, Italy. zara@crs4.it.
authors.forename: Ilenia
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authors.affiliation: Servizio di Epidemiologia, Azienda Sanitaria Locale n. 1, Sassari, Italy. mariobudroni@tiscalinet.it.
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. mariano.dei@irgb.cnr.it.
authors.forename: Mariano
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. sandra.lai@irgb.cnr.it.
authors.forename: Sandra
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. antonella.mulas@irgb.cnr.it.
authors.forename: Antonella
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authors.affiliation: Servizio di Oncologia Medica, Azienda Sanitaria Locale n. 1, Sassari, Italy. olmeo.nina@tiscali.it.
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authors.affiliation: Dipartimento di Oncologia Medica, Azienda Ospedaliero Universitaria, Monserrato, Cagliari, Italy. mtionta@gmail.com.
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authors.affiliation: Dipartimento di Oncologia Medica, Azienda Ospedaliero Universitaria, Monserrato, Cagliari, Italy. francescoatzori74@yahoo.it.
authors.forename: Francesco
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authors.affiliation: Center for Advanced Studies, Research and Development in Sardina (CRS4), Pula, Cagliari, Italy. gmauro@crs4.it.
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authors.forename: Maristella
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. magdalena.zoledziewska@irgb.cnr.it.
authors.forename: Magdalena
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. nazario.olla@irgb.cnr.it.
authors.forename: Nazario
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. mario.lovicu@irgb.cnr.it.
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. manuela.uda@inn.cnr.it.
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authors.forename: Kyriaki
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authors.affiliation: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. dfe20@medschl.cam.ac.uk.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. dfe20@medschl.cam.ac.uk.
authors.forename: Douglas F
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. serena.sanna@irgb.cnr.it.
authors.forename: Serena
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authors.affiliation: Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, 09042, Cagliari, Italy. laura.crisponi@irgb.cnr.it.
authors.forename: Laura
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authors.affiliation: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, Baldinca Li Punti, 07100, Sassari, Italy. gpalmieri@yahoo.com.|Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Traversa La Crucca 3, Baldinca Li Punti, 07100, Sassari, Italy. gpalmieri@yahoo.com.
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mesh_terms: D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins; D006801:Humans; D007558:Italy; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D015534:Trans-Activators
chemical_list: D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2