Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females

Abstract

Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient’s data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients’ biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.

miRNAs in Cancer (Review of Literature)

“…Examination of miRNAs for specific fractions can significantly increase both the sensitivity and specificity of selected circulating miRNAs as noninvasive biomarkers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Unraveling the Role of BRCA1 variants in Dysregulation of Transcriptional and Post-Transcriptional Mechanisms in Breast Cancer

“…Null parity increases the risk of breast cancer, 14 however, in this study 94.4% of patients were parous. Similarly, a study conducted by Ahmed F et al 15 in Pakistan reported 93% breast cancer patients as parous. About 84% patients were breastfeeding their children, contrary to earlier report that breastfeeding for one year reduces breast cancer by 4.3%.…”

“…Pre-menopausal and menopausal patients found in this study were 50.8% and 49.2% respectively. Similarly, Ahmed F et al 15 reported 54.74% cancer in pre-menopausal patients. Patients with a family history of breast cancer were found to have high risk of breast cancer (OR: 4.3186 [1.7336 to 10.7581] p value =0.0017).…”

Breast Cancer in Pakistan - An Updated Overview

“…A study was conducted to predict the correlation of miRNAs with the grade and stage of cancers in population of Pakistan. Effect of miRNA on TGF-beta pathway was studied via TargetScanHuman and correlation was depicted through Mindjet Manager 22 .…”