Polymorphisms in poly (ADP-ribose) polymerase-1 (PARP1) promoter and 3' untranslated region and their association with PARP1 expression in breast cancer patients.
Within the past several years, inhibition of the PARP1 activity has been emerged as one of the most exciting and promising strategies for triple-negative breast cancer (TNBC) therapy. The purpose of this study is to assess PARP1 expression in TNBCs and to evaluate the association between polymorphisms in PARP1 promoter or 3' untranslated region (3'UTR) and PARP1 expression. It was found that PARP1 was overexpressed in nuclear (nPARP1), cytoplasm (cPARP1) and nuclear-cytoplasmic coexisting (coPARP1) of 187 TNBCs in comparison to that of 115 non-TNBCs (nPARP1, p<0.001; cPARP1, p<0.001; coPARP1, p<0.001). High expression of nPARP1 and cPARP1 in breast cancer was related to worse progression-free survival (nPARP1, p=0.007, cPARP1, p=0.003). Additionally, we identified seven published polymorphism sites in the promoter region and in 3'UTR of PARP1 by sequencing. rs7527192 and rs2077197 genotypes were found to be significantly associated with the cPARP1 expression in TNBC patients (rs7527192 AA+GA versus GG, p=0.014; rs2077197 AA+GA versus GG, p=0.041). These findings were confirmed in an independent validation set of 88 TNBCs (rs7527192 GG versus GA+AA, p=0.030; rs2077197 GG versus GA+AA, p=0.030). The PARP1 over-expression including nuclear, cytoplasm and nuclear-cytoplasmic coexisting is a feature of TNBCs and the assessment of its expression may help to predict the efficacy of chemotherapy with PARP1 inhibitor.
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Lili
L
Zhai
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Shuai
S
Li
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Huilan
H
Li
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Yi
Y
Zheng
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Ronggang
R
Lang
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Yu
Y
Fan
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Feng
F
Gu
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China.
Xiaojing
X
Guo
Temple University Hospital Philadelphia, PA, USA.
Xinmin
X
Zhang
Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy; State Key Laboratory of Breast Cancer Research Tianjin, P.R. China ; 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics Tianjin, P.R. China.
Li
L
Fu
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015854:Up-Regulation
D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
3’UTR; PARP1; SNP; TNBC; polymorphism; promoter