title: A DNA repair variant in POLQ (c.-1060A > G) is associated to hereditary breast cancer patients: a case-control study.
abstract: BACKGROUND
  One of the hallmarks of cancer is the occurrence of high levels of chromosomal rearrangements as a result of inaccurate repair of double-strand breaks (DSB). Germline mutations in BRCA and RAD51 genes, involved in DSB repair, are strongly associated with hereditary breast cancer. Pol θ, a translesional DNA polymerase specialized in the replication of damaged DNA, has been also shown to contribute to DNA synthesis associated to DSB repair. It is noteworthy that POLQ is highly expressed in breast tumors and this expression is able to predict patient outcome. The objective of this study was to analyze genetic variants related to POLQ as new population biomarkers of risk in hereditary (HBC) and sporadic (SBC) breast cancer.
  
  
  METHODS
  We analyzed through case-control study nine SNPs of POLQ in hereditary (HBC) and sporadic (SBC) breast cancer patients using Taqman Real Time PCR assays. Polymorphisms were systematically identified through the NCBI database and are located within exons or promoter regions. We recruited 204 breast cancer patients (101 SBC and 103 HBC) and 212 unaffected controls residing in Southern Brazil.
  
  
  RESULTS
  The rs581553 SNP located in the promoter region was strongly associated with HBC (c.-1060A > G; HBC GG = 15, Control TT = 8; OR = 5.67, CI95% = 2.26-14.20; p < 0.0001). Interestingly, 11 of 15 homozygotes for this polymorphism fulfilled criteria for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Furthermore, 12 of them developed bilateral breast cancer and one had a familial history of bilateral breast cancer. This polymorphism was also associated with bilateral breast cancer in 67 patients (OR = 9.86, CI95% = 3.81-25.54). There was no statistically significant difference of age at breast cancer diagnosis between SNP carriers and non-carriers.
  
  
  CONCLUSIONS
  Considering that Pol θ is involved in DBS repair, our results suggest that this polymorphism may contribute to the etiology of HBC, particularly in patients with bilateral breast cancer.
authors.affiliation: Laboratory of Medical Genomics, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. anapaulabrandalize@yahoo.com.br.
authors.forename: Ana Paula Carneiro
authors.initials: AP
authors.lastname: Brandalize
authors.forename: Lavínia
authors.initials: L
authors.lastname: Schüler-Faccini
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hoffmann
authors.forename: Maira
authors.initials: M
authors.lastname: Caleffi
authors.forename: Christophe
authors.initials: C
authors.lastname: Cazaux
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000097462:DNA Polymerase theta
chemical_list: D004259:DNA-Directed DNA Polymerase; D000097462:DNA Polymerase theta