With October being recognized as Breast Cancer Awareness Month, the team at Golden Helix thought it would be appropriate to pay tribute to some of the publications that over the years, have contributed to the many discoveries made in breast cancer diagnosis, prediction, underlying causes, and case management. We are very proud to be a part of cancer research and we are confident that our new product, VSClinical +Cancer Add-on, will prove to be a game-changer for precision medicine in oncology.
Researchers in Canada have been studying a novel breast cancer susceptibility variant on chromosome 4q31.22 locus which has been associated with an overall breast cancer risk in women of European descent. Using SNP & Variation Suite (SVS) software to perform the association analyses, the team was able to report the novel variant which was not previously identified as being associated with an elevated risk for premenopausal breast cancer in women of Caucasian ancestry. This study was able to confirm the elevated risk for premenopausal breast cancer previously identified in Caucasian women, as well as posing a risk to women of African descent. The team identified three potential causal variants using fine-mapping techniques that are strongly associated with premenopausal breast cancer risk and may have enhancer functions effecting nearby genes. Their work was able to open the door for further investigations of potential contributors to premenopausal breast cancer risk.
Sambasivarao Damaraju & Colleagues, University of Alberta / Published in the International Journal of Cancer (2019)
Genetic Variants in Genes Related to Inflammation, Apoptosis and Autophagy in Breast Cancer Risk
Canadian researchers teamed up with researchers from the US to explore how inflammation effects the risk for breast cancer in a population-based study of women of European and East Asian descent. Analyzing single nucleotide polymorphisms (SNP’s) related to inflammation, SVS software was used to perform the statistical analyses. This study included the integration of factors such as body mass index, physical activity and smoking status in order to assess the statistical interactions between the SNP’s and lifestyle choices. Although the results were mixed, their findings support the importance of considering potential environmental interactions in genetic susceptibility models when predicting breast cancer risk.
Angela Brooks-Wilson & Colleagues, British Columbia Cancer Agency / Published in PLOS One (2019)
Taking advantage of the advances in next-generation sequencing and specifically whole-exome sequencing (WES), Brazilian scientists utilized VarSeq software to filter and create a function-based prioritization of variants in their quest to identify new genetic factors of hereditary breast cancer. The goal of this investigation was to use WES to screen breast cancer patients who were lacking the known pathogenic variants which had been previously identified as the major breast cancer-predisposing genes, and to identify the most promising novel hereditary breast cancer genes. The team selected patients to participate that were negative for pathogenic variants in BRCA 1/2, TP53 and CHEK2 c.1100delC. Using 17 selected patients with a history of familial cancer, more than 200,000 variants of interest were originally identified. To prioritize the identified variants, the team applied several filters that focused on quality, frequency, and function. In the end, this study presented the first WES data regarding hereditary breast cancer in South American women and will likely pave the way for many more. It also supports the use of WES for assessing hereditary breast cancer predisposition. I encourage you to read the study in its entirety by clicking on the title. My description does not begin to capture the important elements of the monumental project!
Dirce Carraro & Colleagues, A.C. Camarago Cancer Center, Brazil / Published in Frontiers of Genetics (2018)
Germline Copy Number Variations are Associated With Breast Cancer Risk and Prognosis
In an earlier study conducted at the University of Alberta, the team set out to identify breast cancer-associated copy number variations (CNVs) and how they contribute to disease risk using a genome-wide association (GWAS) design. SVS software was used to perform population stratification during their principal component analysis. The study design consisted of the following steps: Identification of CNV-sncRNAs associated with breast cancer risk; Validation of associated CNVs using TCGA-Breast Cancer dataset; Tissue-specific expression of CNV-sycRNA genes in breast tissue (TCGA); Correlating the sncRNA expression and copy number status and/or Identification of mRNS’s regulated by CNV-miRNAs and their functions; with the final step being the pathway analysis for correlated target genes. Through their investigation, the team was able to identify and validate germline CNVs associated with breast cancer, showing that germline CNVs can potentially influence tissue-level gene expression.
Sambasivarao Damaraju & Colleagues, University of Alberta / Published in Scientific Reports (2017)
In 2015, a research team from the University of California at San Francisco endeavored to unlock the mystery of persistent post-operative pain in women who undergo mastectomy or breast-conserving surgeries. Having published data previously regarding the well-documented cases of persistent pain after breast cancer surgery, the group focused on genotypic factors that would indicate the molecular mechanisms that contribute to the condition. They chose to evaluate the associations between genes that encode for potassium ion channels and self-described pain levels in patients who had undergone breast cancer surgery over a six-month post-operative period. Golden Helix software was used to verify the homogeneity in ancestry among the patients, which minimized confounding data due to population stratification. Although the data indicated that replication of the study is warranted, the study suggests that potassium channel subtypes play a role in the development, maintenance and severity of pain.
Bradley Aouizerat (currently at New York University) & Colleagues, University of California-San Francisco / Published in Pain (2015)
Characterization of Familial Breast Cancer in Saudi Arabia
Also, in 2015, a team from King Abdulaziz University in Saudi Arabia examined the contribution of genetic factors in the development of early-onset breast cancer in a specific population of women from the western region of Saudi Arabia. Using SVS software to help with whole-exome sequencing methodology, the group was able to identify several coding SNPs that were either rare or had not been previously thought to affect genes controlling DNA repair in the BRCA 1/2 pathway. Although this was considered a pilot study and the sample size was small, it was the first to report on the breast cancer predisposition factors in a population strictly from Saudi Arabia, likely providing the template used for subsequent studies based on these initial findings.
Ashraf Dallol & Colleagues, King Abdulaziz University / Published in BMC Genomics (2015)
To access the complete list of publications citing Golden Helix products, please visit our Published Articles page on our website.
From all of us at Golden Helix, we honor those of you have been touched by breast cancer in some way, and those of you who endeavor to fully understand and eradicate this far-reaching disease.