ABSTRACT
The purpose of this study is to assess the effect of consanguinity on breast cancer incidence in Tunisia. We conducted a case-control study to evaluate the involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs according to consanguinity among 40 cases of familial breast cancer, 46 cases with sporadic breast cancer and 34 healthy controls. We showed significant difference in consanguinity rate between breast cancer patients versus healthy controls P = 0.001. Distribution of homozygous BRCA1 haplotypes among healthy women versus breast cancer patients was significantly different; p=0.02. Parental consanguinity seems to protect against breast cancer in the Tunisian population.
Subject(s)
BRCA1 Protein/genetics , Consanguinity , Haplotypes/genetics , Mutation/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Aged , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Case-Control Studies , Female , Follow-Up Studies , Genetic Predisposition to Disease , Heterozygote , Homozygote , Humans , Incidence , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Prospective Studies , Tunisia/epidemiology , Young AdultABSTRACT
INTRODUCTION: MicroRNAs are small, non coding regulatory molecules containing approximately 21 to 25 nucleotides. They function as controllers of expression at post transcriptional levels of most human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study is to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17, miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible interaction in triple-negative and non triple-negative primary breast cancers based on clinical outcome. METHODS: 60 triple-negative and non triple-negative breast cancer cases, along with their corresponding normal samples were investigated in relation to the expression of the seven studied miRNAs using qPCR Syber Green. RESULTS: We observed that miR-21, miR-146a and miR-182 were significantly over expressed in triple negative breast cancer. Moreover, miR-10b, miR-21 and miR-182 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma while only miR-10b was associated with grade III in non triple negative breast cancer cases. Almost all the analyzed microRNAs were strongly associated with patients' genico-obstetric history in non triple negative breast cancer cases except for miR-34a. All the studied microRNAs were strongly correlated with the use of the contraceptive pills in non triple negative breast cancer groups. The additive effect of hormonal factors in triple negative breast cancer cases showed an association with all the studied miRs except for miR-34 and miR-146a. CONCLUSION: The studied microRNAs are strongly influenced by environmental factors especially with hormonal patients' history. Moreover, miR-10b, miR-21 and miR-182 could be defined as biomarkers in breast cancer to predict both lymph node metastases and grade III occurrence.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Ductal, Breast/metabolism , MicroRNAs/metabolism , Triple Negative Breast Neoplasms/metabolism , Adult , Biomarkers, Tumor/genetics , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/therapy , Female , Gene Expression , Humans , MicroRNAs/genetics , Prognosis , ROC Curve , Treatment Outcome , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/therapy , TunisiaABSTRACT
In recent years, circulating miRNAs have attracted interest as stable, non-invasive biomarkers for various pathological conditions. Here, we investigated their potential to serve as minimally invasive, early detection markers for inflammatory breast cancer (IBC) and non-inflammatory breast cancer (non-IBC) in serum. miRNA profiling was performed on serum from 20 patients with non-IBC, 20 with IBC, and 20 normal control subjects. Real-time reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure the level of 12 candidate miRNAs previously identified in other research(miR-342-5p, miR-342--3p, miR-320, miR-30b, miR-29a, miR-24, miR-15a, miR-548d-5p, miR-486-3p, miR-451, miR-337-5p, miR-335).We found that 4 miRNAs (miR-24, miR-342-3p, miR-337-5p and miR-451) were differentially expressed in serum of IBC patients compared to non-IBC, and 3 miRNAs (miR-337-5p ,miR-451and miR-30b) were differentially expressed in IBC and non-IBC patients combined compared to healthy controls. miR-24, miR-342-3p, miR-337-5p and miR-451 were found to be significantly down-regulated in IBC patients compared to non-IBC. Likewise, the expression level of mir-451 showed significant down-regulation in IBC serum, while mir-30b and miR-337-5p were up-regulated in non-IBC serum comparatively to normal controls. Using receiver operational curve (ROC) analysis, we show that dysregulated miRNAs can discriminate patients with IBC and non-IBC from healthy controls with sensitivity ranging from 76 to 81% and specificity from 66 to 80%, for three separate miRNAs. In conclusion, our data suggest that circulating miRNAs are potential biomarkers for classifying IBC and non-IBC, and may also be candidates for early detection of breast cancer.