scholarly journals Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

Oncotarget ◽  
2016 ◽  
Vol 7 (49) ◽  
pp. 80140-80163 ◽  
Author(s):  
Yosr Hamdi ◽  
Penny Soucy ◽  
Véronique Adoue ◽  
Kyriaki Michailidou ◽  
Sander Canisius ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Allelic Expression ◽  
Susceptibility Locus ◽  
Differential Allelic Expression

scholarly journals Single Nucleotide Polymorphism in hsa-mir-196a-2 and Breast Cancer Risk: A Case Control Study

2011 ◽  
Vol 14 (5) ◽  
pp. 417-421 ◽  
Author(s):  
Dominik J. Jedlinski ◽  
Plamena N. Gabrovska ◽  
Stephen R. Weinstein ◽  
Robert A. Smith ◽  
Lyn R. Griffiths
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Case Control ◽  
Cancer Tissue ◽  
Transcriptional Level ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

Birth weight, breast cancer susceptibility loci, and breast cancer risk

2010 ◽  
Vol 21 (5) ◽  
pp. 689-696 ◽  
Author(s):  
Rulla M. Tamimi ◽  
Pagona Lagiou ◽  
Kamila Czene ◽  
Jianjun Liu ◽  
Anders Ekbom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Birth Weight ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Loci

scholarly journals CTLA-4 polymorphisms associate with breast cancer susceptibility in Asians: a meta-analysis

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2815 ◽  
Author(s):  
Zhiming Dai ◽  
Tian Tian ◽  
Meng Wang ◽  
Xinghan Liu ◽  
Shuai Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Large Scale ◽  
Cancer Susceptibility ◽  
Cytotoxic T Lymphocyte ◽  
Meta Analysis ◽  
Breast Cancer Susceptibility ◽  
Breast Cancer Patients ◽  
Link Type

Previous studies have investigated the association between cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms and breast cancer susceptibility, but the results remained inconsistent. Therefore, we evaluated the relationship between four common CTLA-4 polymorphisms and breast cancer risk by a meta-analysis, aiming to derive a comprehensive and precise conclusion. We searched EMBASE, Pubmed, Web of Science, CNKI, and Wanfang databases until July 18th, 2016. Finally, ten eligible studies involving 4,544 breast cancer patients and 4,515 cancer-free controls were included; all these studies were from Asia. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the breast cancer risk in five genetic models. The results indicated that the CTLA-4 +49A>G (rs231775) polymorphism had a significant association with decreased breast cancer risk in allelic, homozygous, dominant and recessive models. Also, the +6230G>A (rs3087243) polymorphism reduced breast cancer risk especially in the Chinese population under homozygous and recessive models. In contrast, the −1661A>G (rs4553808) polymorphism increased breast cancer risk in allelic, heterozygous and dominant models, whereas −1722 T>C (rs733618) did not relate to breast cancer risk. In conclusion, CTLA-4 polymorphisms significantly associate with breast cancer susceptibility in Asian populations, and different gene loci may have different effects on breast cancer development. Further large-scale studies including multi-racial populations are required to confirm our findings.

scholarly journals Aberrant epigenetic and transcriptional events associated with breast cancer risk

2021 ◽  
Author(s):  
Natascia Marino ◽  
Rana German ◽  
Ram Podicheti ◽  
Douglas B. Rush ◽  
Pam Rockey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Epithelial Cells ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Normal Breast ◽  
Breast Tissues

ABSTRACTBackgroundGenome-wide association studies have identified several breast cancer susceptibility loci. However, biomarkers for risk assessment are still missing. Here, we investigated cancer-related molecular changes detected in tissues from women at high risk for breast cancer prior to disease manifestation. Disease-free breast tissue cores donated by healthy women (N=146, median age=39 years) were processed for both methylome (MethylCap) and transcriptome (Illumina’s HiSeq4000) sequencing. Analysis of tissue microarray and primary breast epithelial cells was used to confirm gene expression dysregulation.ResultsTranscriptomic analysis identified 69 differentially expressed genes between women at either high and those at average risk of breast cancer (Tyrer-Cuzick model) at FDR<0.05 and fold change≥2. The majority of the identified genes were involved in DNA damage checkpoint, cell cycle, and cell adhesion. Two genes, FAM83A and NEK2, were overexpressed in tissue sections (FDR<0.01) and primary epithelial cells (p<0.05) from high-risk breasts. Moreover, 1698 DNA methylation aberrations were identified in high-risk breast tissues (FDR<0.05), partially overlapped with cancer-related signatures and correlated with transcriptional changes (p<0.05, r≤0.5). Finally, among the participants, 35 women donated breast biopsies at two time points, and age-related molecular alterations enhanced in high-risk subjects were identified.ConclusionsNormal breast tissue from women at high risk of breast cancer bears molecular aberrations that may contribute to breast cancer susceptibility. This study is the first molecular characterization of the true normal breast tissues and provides an opportunity to investigate molecular markers of breast cancer risk, which may lead to new preventive approaches.

Genetic Identification of Multiple Loci That Control Breast Cancer Susceptibility in the Rat

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 289-299
Author(s):  
Laurie A Shepel ◽  
Hong Lan ◽  
Jill D Haag ◽  
Gerlyn M Brasic ◽  
Megan E Gheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
African American Women ◽  
Mammary Carcinoma ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Chromosome 8 ◽  
Genetic Identification ◽  
Cancer Susceptibility Genes

Abstract We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.

Decreased TGFBR1 signaling and breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1548-1548
Author(s):  
Clark Henegan ◽  
Lakisha Moore-Smith ◽  
Nengjun Yi ◽  
Habibul Ahsan ◽  
Alice S Whittemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Case Control ◽  
Migration And Invasion ◽  
Tgf Beta ◽  
Case Control Studies ◽  
Meta Analyses

1548 Background: We previously identified TGFBR1*6A (rs11466445), a hypomorphic TGF-beta type 1 receptor variant that is associated with cancer risk, has impaired TGF-beta signaling capability, and enhances the migration and invasion of breast cancer cells (Cancer Res 2008, 68:1319). Two recent large meta-analyses of case control studies have found a significant association between TGFBR1*6A and risk of breast cancer (Mol Biol Rep 2010 37:3227; PLoS One 2012,7(8). Rs7034462 is a single nucleotide polymorphism (SNP) in a noncoding region more than 9 kilobases upstream of TGFBR1 exon 1, which has been shown to be associated with decreased TGFBR1 expression similar to TGFBR1*6A (J Exp Clin Cancer Res 2010, 29:57). In this study we tested the hypothesis that rs7034462 may be associated with breast cancer risk. Methods: rs7034462 was genotyped in DNA obtained from patients with breast cancer and their unaffected sisters recruited by the Breast Cancer Family Registry (B-CFR). Results: The median age of cases and controls was 48.8 and 47.6 years, respectively. Using a simple case-control genetic association analysis for this family-matched population, rs7034462 was found to be associated with breast cancer risk. Conclusions: TGFBR1 rs7034462 is emerging as a low penetrance breast cancer susceptibility allele suggesting that two distinct TGFBR1 SNPs, each associated with decreased TGFBR1 expression, may modulate breast cancer risk. [Table: see text]

scholarly journals Development and Validation of a Clinical Polygenic Risk Score to Predict Breast Cancer Risk

2020 ◽  
pp. 585-592 ◽  
Author(s):  
Elisha Hughes ◽  
Placede Tshiaba ◽  
Shannon Gallagher ◽  
Susanne Wagner ◽  
Thaddeus Judkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Cancer History ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Susceptibility Genes

PURPOSE Women with a family history of breast cancer are frequently referred for hereditary cancer genetic testing, yet < 10% are found to have pathogenic variants in known breast cancer susceptibility genes. Large-scale genotyping studies have identified common variants (primarily single-nucleotide polymorphisms [SNPs]) with individually modest breast cancer risk that, in aggregate, account for considerable breast cancer susceptibility. Here, we describe the development and empirical validation of an SNP-based polygenic breast cancer risk score. METHODS A panel of 94 SNPs was examined for association with breast cancer in women of European ancestry undergoing hereditary cancer genetic testing and negative for pathogenic variants in breast cancer susceptibility genes. Candidate polygenic risk scores (PRSs) as predictors of personal breast cancer history were developed through multivariable logistic regression models adjusted for age, cancer history, and ancestry. An optimized PRS was validated in 2 independent cohorts (n = 13,174; n = 141,160). RESULTS Within the training cohort (n = 24,259), 4,291 women (18%) had a personal history of breast cancer and 8,725 women (36%) reported breast cancer in a first-degree relative. The optimized PRS included 86 variants and was highly predictive of breast cancer status in both validation cohorts ( P = 6.4 × 10−66; P < 10−325). The odds ratio (OR) per unit standard deviation was consistent between validations (OR, 1.45 [95% CI, 1.39 to 1.52]; OR 1.47 [95% CI, 1.45 to 1.49]). In a direct comparison, the 86-SNP PRS outperformed a previously described PRS of 77 SNPs. CONCLUSION The validation and implementation of a PRS for women without pathogenic variants in known breast cancer susceptibility genes offers potential for risk stratification to guide surveillance recommendations.

scholarly journals Impact of ESR1 Polymorphisms on Risk of Breast Cancer in the Chinese Han Population

2019 ◽  
Author(s):  
Ying Wei ◽  
Xiaolin Wang ◽  
Zhe Zhang ◽  
Changtao Zhao ◽  
Yuwei Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Genetic Models ◽  
Chinese Han ◽  
Han Population ◽  
Esr1 Gene

Abstract Background The Estrogen receptor-1 (ESR1) gene encodes estrogen receptor-α which is a major biomarker in the development of breast cancer. This research aimed to investigate the effect of ESR1 polymorphisms on breast cancer in Chinese Han women.Methods Four candidate single nucleotide polymorphisms (SNPs) in ESR1 gene among 503 breast cancer patients and 503 healthy people were genotyped using Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratio (OR) and 95% confidence intervals (95% CIs) in four genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1 expression analysis respectively.Results The allele T of rs9383938 in ESR1 was significantly associated with an increased breast cancer risk (OR = 1.26, 95% CI = 1.05 – 1.50, p = 0.013). In genetic models, rs9383938 increased breast cancer risk in codominant model (OR = 1.54, 95% CI = 1.07 – 2.22, p = 0.021), dominant model (OR = 1.31, 95% CI = 1.01 – 1.68, p = 0.040), and additive model (OR = 1.24, 95% CI = 1.04 – 1.48, p = 0.017). Stratification analysis showed that rs9383938 and rs2228480 raised the breast cancer susceptibility at age < 50 years. Rs1801132 of ESR1 was also associated with the status of ER, PR, and Her-2 in allele model and genetic models significantly.Conclusion This study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in Chinese Han population. Further mechanisms studies are needed to confirm the contribution of ESR1.

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