scholarly journals Deciphering the Role of 3D Genome Organization in Breast Cancer Susceptibility

2022 ◽  
Vol 12 ◽  
Author(s):  
Brittany Baur ◽  
Da-Inn Lee ◽  
Jill Haag ◽  
Deborah Chasman ◽  
Michael Gould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genome Organization ◽  
Mammary Epithelial Cells ◽  
Cancer Susceptibility ◽  
Three Dimensional ◽  
Breast Cancer Susceptibility ◽  
Higher Order ◽  
Mammary Epithelial ◽  
3D Genome

Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as the “Window of Susceptibility” (WOS). Rats have a similar WOS for developing breast cancer. A previous study in rat identified an age-specific long-range regulatory interaction for the cancer gene, Pappa, that is associated with breast cancer susceptibility. However, the global role of three-dimensional genome organization and downstream gene expression programs in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside the WOS. To systematically identify higher-order changes in 3D genome organization, we developed NE-MVNMF that combines network enhancement followed by multitask non-negative matrix factorization. We examined three-dimensional genome organization dynamics at the level of individual loops as well as higher-order domains. Differential chromatin interactions tend to be associated with differentially up-regulated genes with the WOS and recapitulate several human SNP-gene interactions associated with breast cancer susceptibility. Our approach identified genomic blocks of regions with greater overall differences in contact count between the two time points when the cluster assignments change and identified genes and pathways implicated in early carcinogenesis and cancer treatment. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may influence susceptibility to breast cancer.

scholarly journals The role of genetic breast cancer susceptibility variants as prognostic factors

2012 ◽  
Vol 21 (17) ◽  
pp. 3926-3939 ◽  
Author(s):  
Peter A. Fasching ◽  
Paul D.P. Pharoah ◽  
Angela Cox ◽  
Heli Nevanlinna ◽  
Stig E. Bojesen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility

Role of GSK3β in breast cancer susceptibility

2017 ◽  
Vol 18 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Andrés Felipe Aristizabal-Pachon ◽  
Willian Orlando Castillo
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility

scholarly journals The role of Prolactin/Prolactin Receptor polymorphisms and expression in breast cancer susceptibility and outcome

2020 ◽  
Vol 9 (10) ◽  
pp. 6344-6353
Author(s):  
Doonyapat Sa-nguanraksa ◽  
Cholladda Thasripoo ◽  
Norasate Samarnthai ◽  
Tanawan Kummalue ◽  
Thanawat Thumrongtaradol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Prolactin Receptor ◽  
Breast Cancer Susceptibility

scholarly journals The role of E-cadherin - 160C/A polymorphism in breast cancer

2016 ◽  
Vol 11 (1) ◽  
pp. 110-115 ◽  
Author(s):  
Gaojian Luo ◽  
Diyu Huang ◽  
Ran Tao ◽  
Jianfeng Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Susceptibility ◽  
Short Review ◽  
Breast Cancer Susceptibility ◽  
Primary Lesion ◽  
Cell Dedifferentiation ◽  
Adhesion System ◽  
E Cadherin

AbstractBreast cancer is the most prevalent cancer in women worldwide. Numerous studies have suggested that the E-cadherin adhesion system is dysregulated in cancer cells. These impaired functions of E-cadherin contribute to releasing cancer cells from the primary lesion to cell dedifferentiation. Some studies have shown that polymorphism may affect E-cadherin expression, and then play a role in susceptibility to breast cancer. However, the results remained controversial. In this short review, we summarize the functions of E-cadherin and the signaling pathways it regulates, and assess the association between CDH1 polymorphisms and breast cancer susceptibility. This study suggests that genetic variation in CDH1 and -160C/A polymorphism may have an association with breast cancer risk. The assessment of CDH1 polymorphisms may be used for the identification of patients suitable for anti- CDH1 therapy.

scholarly journals The Role of BRCA1/2-Mutated Tumor Microenvironment in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 575
Author(s):  
Svetlana Miklikova ◽  
Lenka Trnkova ◽  
Jana Plava ◽  
Martin Bohac ◽  
Marcela Kuniakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Aggressive Behavior ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Clinical Observations ◽  
High Incidence ◽  
High Incidence Rate ◽  
Worse Prognosis

Taking into account the factors of high incidence rate, prevalence and mortality, breast cancer represents a crucial social and economic burden. Most cases of breast cancer develop as a consequence of somatic mutations accumulating in mammary epithelial cells throughout lifetime and approximately 5–10% can be ascribed to monogenic predispositions. Even though the role of genetic predispositions in breast cancer is well described in the context of genetics, very little is known about the role of the microenvironment carrying the same aberrant cells impaired by the germline mutation in the breast cancer development and progression. Based on the clinical observations, carcinomas carrying mutations in hereditary tumor-suppressor genes involved in maintaining genome integrity such as BRCA1/2 have worse prognosis and aggressive behavior. One of the mechanisms clarifying the aggressive nature of BRCA-associated tumors implies alterations within the surrounding adipose tissue itself. The objective of this review is to look at the role of BRCA1/2 mutations in the context of breast tumor microenvironment and plausible mechanisms by which it contributes to the aggressive behavior of the tumor cells.

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