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Recent advances in whole-genome association studies WGASs for human cancer source are beginning to provide the part lists of low-penetrance susceptibility genes.

However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined.

We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence.

National Center for Biotechnology InformationU. Parabens are absorbed through the skin, and they have been found in biopsy samples from breast tumours. Alternate a drink of water or cola between alcoholic beverages, so you reduce the total amount of alcohol you drink. Parabens, which are preservatives used in many pharmaceutical and cosmetic products, are also source researched as a potential risk for breast cancer.

First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk.

This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional effects of candidate genes and proteins. National Center for Biotechnology InformationU. Didn't get the message?

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Add to My Bibliography. Generate a file for use with external citation management software. Images from this publication. See all images 7 Free text. Strategy for candidate gene prioritization in WGAS results.

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To obtain this information at the genome-wide level, we propose first to use GO terms to examine the WGAS rank for asymmetries in biological processes.

These asymmetries will then be used to guide the analysis of omic data sets relevant to breast cancer biology. Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes. WGAS rank asymmetries for specific biological processes.

Top left panel, results of the analysis of the WGAS rank according to the lowest P value per gene locus. Differences are always shown from top to bottom, so the top shows over-representation in the GO terms Transport and Cell Communication.

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Graphics show significant partitions. Bottom left panel, graphical representation of the positions of genes annotated with GO terms distributed asymmetrically in the WGAS P value rank.

However, the evidence shows that if you exercise regularly at this stage of your life, you will have a substantially lower risk of developing breast cancer in the future. However, scientists disagree about the results of these studies and more research continues to be done. These asymmetries will then be used to guide the analysis of omic data sets relevant to breast cancer biology.

The graphical representation of gene positions shows clear differences between Cell Adhesion and more complex patterns — perhaps with different gene subgroups — for Cell Communication and Metabolic processes. Left panel, child terms of Cell Communication Signal TransductionTransport Ion Transport and Cell Adhesion rest of terms shown in the inset are over-represented at P values of up to 0.

Asymmetries in biological evidence of breast cancer. An example of the results of applying the methodology used to examine the WGAS ranks to a breast cancer biological evidence data set. This analysis identifies the association between gene expression levels and patient survival or prognosis measured by the hazard ratio HR.

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Importantly, the association between cell proliferation and poor prognosis has been demonstrated in previous studies using different approaches [-]. Asymmetries for Cell Communication and Cell Adhesion. Of the biological evidence of breast cancer examined in this study, three cases showed asymmetries in biological processes that are similar to those observed in the WGAS ranks.

Three cases showed similar asymmetries for Cell Adhesion: On the basis of these results, all three ranks were inverted and combined for comparison with the WGAS results. Combination of breast cancer biology evidence and evaluation of WGAS results for priorization of candidate low-penetrance susceptibility genes.

Same biological processes in the interactome network neighborhoods.

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Right panel, distribution of all possible short paths in the giant network component. The x-axis represents the cumulative percentage up to Functional effects and associations between candidates and benchmarks. Left panel, network of transcriptional perturbations mediated by SNPs at gene loci. To avoid bias, we excluded those SNPs that are not annotated in the original data set of Dixon and colleagues [].

Right panels, network results of the analysis of randomly chosen sets of 50 genes and the same benchmarks histograms and curves compared to the observed values in the left panel vertical arrowsfor connected nodes top or edges bottom. How to cite this comment: Supplemental Content Full text links.

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