La méthylation de l'ADN dans les tissus mammaires normaux et le risque de cancer du sein controlatéral

Authors: Issa, Elissar
Advisor: Diorio, CarolineDurocher, Francine
Abstract: INTRODUCTION: Women with breast cancer (BC) have an increased risk of developing a contralateral breast cancer (CBC). This risk is 3 to 5 times higher than the risk of developing primary breast cancer by women in the general population. The methylation of DNA is known to be involved in the development of cancer, and changes in methylation profile in breast tumor cells have already been observed. OBJECTIVE: Our aims are to identify changes in global DNA methylation as well as the differentially methylated sites that are associated with an increased risk of developing CBC. METHODS: This is a case-control study (1:1) nested in a cohort of 1242 women. Cases (n = 20) were diagnosed with CBC during follow-up but not Controls (n = 20). Cases were matched to controls for CSC risk factors such as year of surgery, age, family history of BC, and the treatment. The DNA was extracted from normal breast tissue (to minimize field effect) more than 1 cm from the paraffin-embedded tumor and the methylation was measured by Illumina Infinium 450K. RESULTS: Global DNA hypomethylation was associated with a decreased risk of CBC with an odd ratios and a confidence interval at 95% = 0.714 (0.227-2.251), but this association was not significant. In addition, non-significant hypomethylation in 3'UTR and intergenic regions was observed in cases compared with controls. We have also found hypermethylation of the ELOVL6, DACT2, LHX2, GABRA5 and OSBP2 genes that may be associated with the risk of developing CBC. CONCLUSION: Global DNA hypomethylation from adjacent normal tissues may be predictive of the risk of CBC. In addition, hypermethylation of specific genes such as CCDC108, ELOVL6, DACT2, LHX2, GABRA5 and OSBP2 in normal breast tissues may therefore be useful as a clinical biomarker of CBC if our results were validated in a larger cohort.
Document Type: Mémoire de maîtrise
Issue Date: 2018
Open Access Date: 23 May 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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