scholarly journals Effects of FGFR1 Gene Polymorphisms on the Risk of Breast Cancer and FGFR1 Protein Expression

2018 ◽  
Vol 47 (6) ◽  
pp. 2569-2578 ◽  
Author(s):  
Junqiang Wu ◽  
Yuhang Wang ◽  
Jing Liu ◽  
Qianlin Chen ◽  
Da Pang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Protein Expression ◽  
Cox Regression ◽  
Cancer Susceptibility ◽  
Growth Factor Receptor ◽  
Breast Cancer Susceptibility ◽  
Cancer Prognosis ◽  
Nucleotide Polymorphisms

Background/Aims: Fibroblast growth factor receptor 1 (FGFR1) is widely considered to play an important role in mammary carcinogenesis. Some common variants in FGFR1 might be associated with its expression, and further affect breast cancer risk. The aim of this study was to investigate effects of single-nucleotide polymorphisms (SNPs) in FGFR1 on breast cancer susceptibility and FGFR1 protein expression. Methods: SNPs rs17182023, rs17175624 and rs10958704 in FGFR1 were genotyped in 747 breast cancer cases and 716 healthy controls by SNaPshot method. The associations between SNPs and breast cancer were examined by logistic regression. Immunohistochemistry(IHC) was used to detect FGFR1 protein expression, and the association of FGFR1 polymorphisms with its protein expression was analyzed by Pearson’s chi-square test. Additionally, Cox regression and Kaplan-Meier analysis was used to evaluate the association between FGFR1 protein expression and breast cancer prognosis. Results: The minor allele of rs17182023 in FGFR1 was significantly associated with reduced breast cancer risk, with an odds ratio of 0.800 (95%CI = 0.684-0.935). No significant associations were detected between other SNPs and breast cancer. Moreover, rs17182023 was correlated to FGFR1 protein expression (P = 0.006), and patients with high FGFR1 protein expression tended to have poor outcomes. Conclusions: SNP rs17182023 was correlated to reduced breast cancer risk, and was associated with FGFR1 protein expression. High FGFR1 protein expression was an independent risk factor of breast cancer, and resulted in poor prognosis.

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.

scholarly journals The development of rs7107217 genotyping method and initial study of the association of this gene with the breast cancer risk in Vietnamese women

2019 ◽  
Vol 2 (5) ◽  
pp. 40-49
Author(s):  
Thanh Thi Ngoc Nguyen ◽  
Giau Thi Ngoc Mai ◽  
Hue Thi Nguyen
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Regulation Of Gene Expression ◽  
High Sensitivity ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Cancer Susceptibility Genes ◽  
And Control

Breast cancer is the most common cancer for women around the world. The presence of single nucleotide polymorphisms (SNP) on or near the coding region of breast cancer susceptibility genes can affect the regulation of gene expression, which may increase or decrease the risk of breast cancer. BARX2 was showed to stimulate the expression of ERS1, which involved in the development of breast cancer. SNP rs7107217 on 152kb downstream of the BARX2 could affect the level of protein BARX2 and had been proved to associate with the breast cancer risk in populations similar to Vietnamese, including Chinese and Korean. In this study, rs7107217 was genotyped and initially detemined the association with the breast cancer risk in Vietnamese. Real-time PCR HRM was optimized and used to genotype rs7107217 in 117 breast cancer cases and 105 healthy controls. Thereafter, the correlation of this SNP with the risk of breast cancer was initially determined by analyzing the differences in allelic and genotypic frequencies between cases and control groups. The results showed the optimal rs7107217 genotyping condition was successfully developed with the high sensitivity, specificity, and consistency. SNP rs7107217 had high polymorphism with the frequency of minor allele C of 29.9% and 35.3% in case and control, respectively. SNP rs7107217 had been found no association with the breast cancer risk (C vs A: P = 0.23, OR (95% CI) = 0.79 (0.53 – 1.17)). However with the low reliability of the analysis (11.71%) and the high potential related to the formation of breast cancer, the association between rs7107217 and breast cancer risk in Vietnamese population should be further conducted on a larger sample size to get higher accuracy.

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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