Genetic polymorphism and expression of HSF1 gene is significantly associated with breast cancer in Saudi females

Abstract

The transcription factor, heat shock factor 1 (HSF1), influences the expression of heat shock proteins as well as other activities like the induction of tumor suppressor genes, signal transduction pathway, and glucose metabolism. We hypothesized that single nucleotide polymorphisms (SNPs) in HSF1 gene might affect its expression or function which might have an influence on the development of breast cancer. The study group included 242 individuals (146 breast cancer patients and 96 healthy controls). From the cancer patients, genomic DNA was extracted from 96 blood samples and 50 Formalin-Fixed Paraffin Embedded (FFPE) tissues, while from the controls DNA were extracted from blood only. Genotype was carried out for four SNPs in the HSF1 gene (rs78202224, rs35253356, rs4977219 and rs34404564) using Taqman genotyping assay method. The HSF1 expression was investigated using immunohistochemistry on FFPE tissues (cancer tissue and adjacent normal tissue). The SNP rs78202224 (G>T) was significantly associated with increased risk of breast cancer. The combined TT + GT genotype (OR: 6.91; p: 0.035) and the T allele showed high risk (OR: 5.81; p:0.0085) for breast cancer development. The SNP rs34404564 (A>G) had a protective effect against the development of breast cancer. The genotype AG (OR: 0.41; p = 0.0059) and GG+AG (OR: 0.52; p: 0.026) occurred at a significantly lower frequency in the breast cancer patients compared to the frequency in healthy controls. No significant relationship was identified between either rs35253356 (A>G) or rs4977219 (A>C) and breast cancer in Saudi. The HSF1 protein expression was higher in all invasive and in situ breast carcinoma compared to the normal tissue. A stronger positive staining for HSF1 was found in the nucleus compared to the cytoplasm. Our results show that HSF1 gene expression is elevated in breast cancer tissue and two of the studied SNPs correlate significantly with cancer development.

FAM3C‐YY1 axis is essential for TGFβ‐promoted proliferation and migration of human breast cancer MDA‐MB‐231 cells via the activation of HSF1

“…21,22 Heat shock factor 1 is also activated in breast cancer tissue, and its high expression level is associated with poor prognosis of breast cancer. 23,24 Clearly, both FAM3C and HSF1 are important biomarkers and potential targets for the diagnosis and treatment of breast cancer.…”

Male infertility is not liked with HSF1, HSF2 and UBE2I gene polymorphisms among Indian subjects

“…On the basis of the genotypic analysis of our findings, we could not find any relationship between rs78202224 (C>A), rs139496713 (C>T) and rs45504694 (C>A) SNPs in HSF1 and HSF2 genes and male infertility. However, a association of rs78202224 of HSF1 was observed by Almotwaa et al (2018) with breast cancer in Saudi females. On the other hand, Bridges et al (2015) described 34 variants in the exonic sequence of human HSF1 gene and tried to analyse their biological consequences in human diseases [13,17].…”

“…Many genetic association studies have documented the potential impact of HSF1 and HSF2 on human health and diseases and tried to connect HSF1 gene variants and its altered levels, to schizophrenia, bipolar disorder, attention deficit hyperactivity disorder and breast cancer [14][15][16][17]. In the same way, low level of HSF2 mRNA was also observed in different types of malignancies in humans like invasive breast carcinoma, prostate carcinoma and various other carcinomas [16][17][18]. Moreover, UBE2I gene also plays an important role in progression of several cancers as lung, breast and bladder carcinoma [19,20].…”

Bayesian differential analysis of gene regulatory networks exploiting genetic perturbations

“…Specifically, BTF3 was confirmed aberrantly in various cancer tissues such as gastric cancer tissues [47,48], prostate cancer tissues [49], colorectal cancer tissues [50] and pancreatic cancer cells [51]; RPS16 was found dysregulated in disc degeneration, which is one of the main causes of low back pain [52]; HSF1 influenced the expression of heat shock proteins as well as other activities like the induction of tumor suppressor genes, signal transduction pathway, and glucose metabolism. Its associations with gastric cancer [53], breast cancer and two of the studied SNPs correlated significantly with cancer development [54] have been proved; RPS6 was declared closely relevant to the nonsmall cell lung cancer (NSCLC) [55], the renal cell carcinoma [56] and some other cancers [57,58]; MAPKAPK2 was demonstrated to contribute to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis [59].…”