The association of DNA Repair with breast cancer risk in women. A comparative observational study

Jaime Matta,Santos Santiago Medina,Joaquín Laboy,Guillermo Bolaños,Julie Dutil,Jose Ortiz Rosado,Ricardo Barnes,Miguel Echenique,Carolina Alvarez-Garriga,Wanda Vargas,Esperanza Negron,Manuel Bayona,Luisa Morales,Eduardo Ramírez Lizardi,F Sánchez Gaetan ,R Bermejo Martínez ,Erick Suárez ,J Gonzalez De La Cruz ,Ángel Valdivia Romero ,A Torres

doi:10.1186/1471-2407-12-490

Abstract

BackgroundPrevious studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case–control epidemiological study in a Hispanic community.MethodsWe conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously.ResultsCompared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% (p < 0.0001).ConclusionsOur results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

Highlights

Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk
DRC was measured in lymphocytes by a host reactivation assay with a luciferase reporter gene
That initial DRC study consisted of a small sample size (n = 36 patients) and did not have the benefit of ROC analysis or a well-defined percent DRC level as a breast cancer (BC) risk estimator compared to the analyses presented in this study

Summary

Introduction

Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Aging is not the only cause of genomic instability that can lead to cancer. Individuals vary in their inherent sensitivities to mutagens and carcinogens due to differences in their DNA repair capacity (DRC) levels [5]. Epidemiological studies using functional repair assays in lymphocytes have demonstrated that DRC varies greatly among individuals, and that a low DRC is a significant risk factor for the development of several types of cancer [9,12,14,17,19,20,21]

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