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 Germline breast cancer susceptibility genes, tumor characteristics, and survival

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peh Joo Ho ◽  
Alexis J. Khng ◽  
Hui Wen Loh ◽  
Weang-Kee Ho ◽  
Cheng Har Yip ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Tumor Characteristics ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Cancer Susceptibility Genes

Abstract Background Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

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 OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Kashif Ali ◽  
Ishrat Mahjabeen ◽  
Maimoona Sabir ◽  
Humera Mehmood ◽  
Mahmood Akhtar Kayani
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Splice Site ◽  
Nonsense Mutation ◽  
Mutational Analysis ◽  
Germ Line ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Increased Risk

In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly (p<0.001) increased (~29 fold) breast cancer risk was associated with a splice site variant g.9800972T>G and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold) increase in breast cancer risk was associated with g.9793680G>A (p<0.009). Similarly ~14-fold increased risk was associated with Val159Gly (p<0.01), ~17-fold with Gly221Arg (p<0.005), and ~18-fold with Ser326Cys (p<0.004) in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p<0.01) increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer.

scholarly journals Relationship of Breast Cancer Susceptibility with Rs6257 and Rs6258 Polymorphisms in the SHBG Gene

2020 ◽  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Menopausal Status ◽  
Fold Increase ◽  
Sex Hormone Binding Globulin ◽  
Case Group ◽  
Target Cells ◽  
Breast Cancer Patients

Background: Breast cancer is a hormone-dependent malignancy. Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Objective: The present study aimed to assess the relationship between rs6257 and rs6258 polymorphisms in the SHBG gene with breast cancer risk. Materials and Methods: This case-control study was conducted on 100 breast cancer patients and 100 healthy control subjects. After extracting DNA from peripheral blood, Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The data were analyzed in SPSS software using the chi-square test and logistic regression to distinguish the difference between the cases and controls in terms of the distribution of allele types and genotypes. Results: The frequencies of Rs6257 were 78%, 17%, 5% in the case group and 88%, 7%, and 5% in control groups for TT, CC, and CT genotypes respectively. The rs6257 CC genotype showed about a 2.721-fold increase in breast cancer (P=0.030, OR:2.721, CI95%:1.075-6.887). This genotype was reversely associated with age, body mass index, menopausal status, and breast cancer. Nonetheless, Rs6258 had no significant correlation with breast cancer risk or other demographic factors. Conclusions: As evidenced by the obtained results, the rs6257 polymorphism may be a useful biomarker associated with breast cancer risk in Iranian women. To confirm the findings of the present study, larger studies are needed in the future.

scholarly journals Associations between ADIPOQ rs2241766 SNP and breast cancer risk: a systematic review and a meta-analysis

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Xue Hu ◽  
Chunguo Cui ◽  
Tong Sun ◽  
Wan Wang
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Large Scale ◽  
Meta Analysis ◽  
Cochrane Library ◽  
P Value ◽  
China National Knowledge Infrastructure ◽  
Knowledge Infrastructure ◽  
Potential Association

Abstract Purpose We aimed to conduct a meta-analysis to accurately evaluate the potential association between ADIPOQ rs2241766 gene SNP and breast cancer risk. Methods A systematic literature search on Cochrane Library, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) identified 8 articles with 1692 cases and 1890 controls. Strength of association was evaluated by pooled odds ratio (OR), 95 % confidence interval (CI) and p value. Funnel plots and Begger’s regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0. Results The meta-analysis results indicated that the ADIPOQ rs2241766 gene polymorphism did not significantly associated with the risk of breast cancer for these genetic models (TT vs. TG + GG: OR = 1.20, 95 % CI = 0.77–1.89, p=0.417; TT + TG vs. GG: OR = 1.05, 95 % CI = 0.71–1.56, p=0.805; T vs. G: OR =1.17, 95 % CI = 0.79–1.74, p=0.437). Conclusions This study indicated that no significant relationship between the ADIPOQ rs2241766 SNP and breast cancer. Further large-scale and well-designed studies will be indispensable to confirm our result.

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]

Sign in / Sign up

Export Citation Format

Share Document