A DNA repair variant in POLQ (c.-1060A > G) is associated to hereditary breast cancer patients: a case-control study

被引：12
作者：
Carneiro Brandalize, Ana Paula [1 ,3 ,4 ]
Schueler-Faccini, Lavinia [2 ,4 ]
Hoffmann, Jean-Sebastien [5 ,6 ]
Caleffi, Maira [7 ]
Cazaux, Christophe [5 ,6 ]
Ashton-Prolla, Patricia [1 ,2 ,4 ]
机构：
[1] Hosp Clin Porto Alegre, Expt Res Ctr, Lab Med Genom, Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil
[3] Univ Caxias Sul, Lab Genom Prote & DNA Repair, Caxias Do Sul, Brazil
[4] INAGEMP, Inst Nacl Genet Med Populac, Porto Alegre, RS, Brazil
[5] Toulouse Oncopole, CRCT, CNRS ERL 5294, Equipe Labellisee Ligue Canc 2013,INSERM Unit 103, Toulouse, France
[6] Univ Toulouse, UPS, F-31077 Toulouse, France
[7] Hosp Moinhos Vento, Porto Alegre, RS, Brazil
来源：
BMC CANCER | 2014年 / 14卷
关键词：
POLQ; DNA repair; Breast cancer; Translesional DNA polymerase; SNP; POLYMERASE-THETA POLQ; BASE EXCISION-REPAIR; TRANSCRIPTION FACTOR YY1; GENOMIC INSTABILITY; UP-REGULATION; IN-VITRO; BRCA1; REPLICATION; MUTATION; DAMAGE;
D O I：
10.1186/1471-2407-14-850
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 theta, 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. 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.
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页数：7
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