Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes: Triple Negative Breast Cancer Shows Lowest Repair
Department of Basic Sciences, Divisions of Pharmacology, Toxicology, Biochemistry and Cancer Biology, Ponce Health Sciences University—School of Medicine, Ponce Research Institute, Ponce 00716-2348, Puerto Rico
Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico, Medical Sciences Campus, San Juan 00936-5067, Puerto Rico
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(7), 1505; https://doi.org/10.3390/ijms18071505
Received: 21 June 2017 / Revised: 6 July 2017 / Accepted: 7 July 2017 / Published: 12 July 2017
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action)
Breast cancer (BC) is a heterogeneous disease which many studies have classified in at least four molecular subtypes: Luminal A, Luminal B, HER2-Enriched, and Basal-like (including triple-negative breast cancer, TNBC). These subtypes provide information to stratify patients for better prognostic predictions and treatment selection. Individuals vary in their sensitivities to carcinogens due to differences in their DNA repair capacity (DRC) levels. Although our previous case-control study established low DRC (in terms of NER pathway) as a BC risk factor, we aim to study this effect among the molecular subtypes. Therefore, the objectives of this study include investigating whether DRC varies among molecular subtypes and testing any association regarding DRC. This study comprised 267 recently diagnosed women with BC (cases) and 682 without BC (controls). Our results show a substantial variability in DRC among the molecular subtypes, with TNBC cases (n = 47) having the lowest DRC (p-value < 0.05). Almost 80 percent of BC cases had a DRC below the median (4.3%). Low DRC was strongly associated with the TNBC subtype (OR 7.2; 95% CI 3.3, 15.7). In conclusion, our study provides the first report on the variability among the molecular subtypes and provides a hypothesis based on DRC levels for the poor prognosis of TNBC.