title: Association of PALB2 sequence variants with the risk of familial and early-onset breast cancer in a South-American population.
abstract: BACKGROUND
  Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer (BC) in several populations. Nevertheless its contribution in the South-American population is unknown. The goal of this study was to determine the prevalence of PALB2 mutations in the Chilean population.
  
  
  METHODS
  100 Chilean BRCA1/2-negatives familial BC cases were included for the PALB2 mutation analysis. We use conformational sensitive gel electrophoresis and direct sequencing. Using a case-control design, we studied the identified variants in 436 BC cases and 809 controls to evaluate their possible association with BC risk.
  
  
  RESULTS
  No pathogenic mutations were detected. We identified three variants, the variant c.1861C > A not previously described was found in one of the 436 cases and none of the 809 controls. The bioinformatic analyses indicate that this variant probably is not pathogenic. PALB2 c.1676A > G (rs152451A/G) and c.2993C > T (rs45551636C/T) variants were significantly associated with increased BC risk only in cases with a strong family history of BC (OR = 1.9 [CI 95% 1.3-2.8] p < 0.01 and OR = 3.3 [CI 95% 1.4-7.3] p < 0.01, respectively). The rs152451A/G-rs45551636C/T composite genotype produce increase of the BC risk in cases with a strong family history of BC (OR = 3.6 [CI 95% 1.7-8.0] p = 0.003). The rs152451-G/rs45551636-C and rs152451-G/rs45551636-T haplotypes were associated with an increased BC risk only in cases with a strong family history of BC (OR = 1.6 [CI 95% 1.0-2.5] p = 0.05 and OR = 3.7 [CI 95% 1.8-7.5] p < 0.001, respectively).
  
  
  CONCLUSIONS
  Our results suggest that PALB2 c.1676A > G and c.2993C > T play roles in BC risk in women with a strong family history of BC.
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. yessica.leyton@gmail.com.
authors: Yessica
authors: Y
authors: Leyton
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. pgonzalez@med.uchile.cl.
authors: Patricio
authors: P
authors: Gonzalez-Hormazabal
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. rblanco@med.uchile.cl.
authors: Rafael
authors: R
authors: Blanco
authors: National Cancer Society (Corporación Nacional del Cáncer -CONAC-), Santiago, Chile. tbc_conac@edu.tie.cl.
authors: Teresa
authors: T
authors: Bravo
authors: Research Institute in Dental Sciences, School of Odontology, University of Chile, Sergio Livingstone Pohlhammer 943, Santiago, Chile. ramiresfernandez@gmail.com.
authors: Ricardo
authors: R
authors: Fernandez-Ramires
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. seba.morales.p@gmail.com.
authors: Sebastian
authors: S
authors: Morales
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. natalialanderos@udec.cl.
authors: Natalia
authors: N
authors: Landeros
authors: Clínca Las Condes, Santiago, Chile. jmreyes@clc.cl.
authors: Jose M
authors: JM
authors: Reyes
authors: Clínca Las Condes, Santiago, Chile. operalta@med.uchile.cl.|Department of Gyneacology and Obstetrics, School of Medicine, University of Chile, Av Santa Rosa 1234, Santiago, Chile. operalta@med.uchile.cl.
authors: Octavio
authors: O
authors: Peralta
authors: Cell Transformation Laboratory, Institute of Biomedical Sciences (ICBM), School of Medicine, Unversity of Chile, Av. Independencia 1027, Santiago, Chile. jtapia@med.uchile.cl.
authors: Julio C
authors: JC
authors: Tapia
authors: Clínica Santa María, Santiago, Chile. fgomez@csm.cl.
authors: Fernando
authors: F
authors: Gomez
authors: Clínica Santa María, Santiago, Chile. ewaugh@csm.cl.
authors: Enrique
authors: E
authors: Waugh
authors: Clínica Dávila, Av. Recoleta 464, Santiago, Chile. gibanez@cancerdemama.cl.|Hospital San José, San José 1196, Santiago, Chile. gibanez@cancerdemama.cl.
authors: Gladys
authors: G
authors: Ibañez
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. jpakomiob@gmail.com.
authors: Janara
authors: J
authors: Pakomio
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. gvgrau@gmail.com.
authors: Gilberto
authors: G
authors: Grau
authors: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. ljara@med.uchile.cl.
authors: Lilian
authors: L
authors: Jara
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D002677:Chile / Q000453:epidemiology; D019295:Computational Biology; D004252:DNA Mutational Analysis; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011159:Population Surveillance; D015995:Prevalence; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
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