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.

中文翻译：

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对乳腺癌危险因素的感知：巴基斯坦女性 TGF-β/miRNA 轴的失调。

乳腺癌对全世界女性构成严重的健康风险。在亚洲人群中，巴基斯坦女性患乳腺癌的风险最高。在巴基斯坦，九分之一的女性被诊断出患有乳腺癌。导致乳腺癌的病因和危险因素在很大程度上是未知的。在当前的研究中，研究了与巴基斯坦人群最相关的风险因素、肿瘤进展的病因、分子机制和乳腺癌的治疗靶点。一项相关的、横断面的、描述性的和基于问卷的研究旨在预测乳腺癌患者的危险因素。浸润性导管癌 (90%) 和 II 级肿瘤 (73.2%) 形成在我们患者的数据集中更为常见。临床参数，如平均年龄 47.5 岁 (SD ± 11.17)，月经周期紊乱 (> 2)、表亲结婚 (重复) 和哺乳期 (< 0.5 Y) 以及压力、饮食和环境因素在乳腺癌的发展中起着至关重要的作用。除此之外，还进行了计算机分析以使用 TargetScanHuman 筛选调节 TGF-β 通路的 miRNA，并通过 Mindjet Manager 描述相关性。由此获得的信息在乳腺癌临床样本中的外周血单核细胞和活组织检查中通过定量实时 PCR 观察到。TGF-β1 信号通路和 miRNA（miR-29a、miR-140 和 miR-148a）在级别和阶段的患者活检中存在显着失调（**P>0.001），具体与血液样本。miRNA（miR-29a 和 miR-140，miR-148a) 可以成为有效的诊断和预后标志物，因为它们分别调节乳腺癌血液和活检样本中 SMAD4 和 SMAD2 的表达。因此，可以考虑负调控的级联基因和合并的 miRNA 来设计积极的治疗策略，以更好地控制乳腺癌。