Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry

Wang, Shengfeng; Qian, Frank; Zheng, Yonglan; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Wang, Zheng; Blot, William J.; Nathanson, Katherine L.; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Olopade, Olufunmilayo I.; Huo, Dezheng

doi:10.1007/s10549-017-4638-1

Cited by 44 publications

(60 citation statements)

References 30 publications

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“…Previous studies on breast cancer found that risk stratification models could perform differently for patients with various family histories of tumor. 41 , 42 Familial risks could reflect the shared genetic susceptibility and similar exposures to environmental risk factors and have been reported to be associated with esophageal carcinogenesis and prognosis. 43 Patients could benefit from risk evaluation that involves collection of detailed information on clinical risk factors.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Intratumoral and Peritumoral Computed Tomography Radiomics for Predicting Pathological Complete Response to Neoadjuvant Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma

et al. 2020

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Key Points Question Are peritumoral radiomics features extracted from pretreatment computed tomography images predictive of pathological complete response following neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma? Findings In this diagnostic study of 231 patients, the developed model integrating intratumoral and peritumoral radiomics features achieved improvement of predictive performance (area under the receiver operating characteristic curve, 0.852) compared with the conventionally constructed model merely using intratumoral radiomics features (area under the receiver operating characteristic curve, 0.730). Meaning Peritumoral radiomics may provide additional predictive value for treatment response estimation in esophageal squamous cell carcinoma and thus benefit individualized therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Assessment of Intratumoral and Peritumoral Computed Tomography Radiomics for Predicting Pathological Complete Response to Neoadjuvant Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma

et al. 2020

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“…Evidence is accumulating that relying solely on populations of European descent results in an incomplete or inaccurate representation of the genetic susceptibility to cancers (27). For example, replication of risk loci found in European populations through GWAS in multiethnic cohorts has revealed that risk factors may differ in their nature and magnitude of effect (33). The recent increases in the inclusion of non-European populations in GWAS has been mostly attributed to an increase in representation of Asian populations and collectively, African, Hispanics/Latinos, and native or indigenous populations represented less than 4% of the 35 million samples included in 2,500 studies reported in the GWAS catalog (34).…”

Section: Limited Cancer Research In Diverse Populationsmentioning

confidence: 99%

“…Interestingly, a Latina breast cancer GWAS identified a protective variant of Indigenous American origin at the 6q25 locus, which acts independently of the previously known risk variants at this locus (50). Thus, variants associated with risk may not validate in other populations, or even change the direction of risk association (33). Importantly, polygenic risk scores for stratifying women based on their inherited risk of developing breast cancer, which have been developed using data derived largely from European population GWAS, perform poorly in African-American populations as a consequence of inverse directionality of 30%-40% of the susceptibility loci (33).…”

Section: Ancestral-related Health Disparities In Cancer: Breast Cancermentioning

confidence: 99%

An Interactive Resource to Probe Genetic Diversity and Estimated Ancestry in Cancer Cell Lines

et al. 2019

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Recent work points to a lack of diversity in genomics studies from genome-wide association studies to somatic (tumor) genome analyses. Yet, population-specific genetic variation has been shown to contribute to health disparities in cancer risk and outcomes. Immortalized cancer cell lines are widely used in cancer research, from mechanistic studies to drug screening. Larger collections of cancer cell lines better represent the genomic heterogeneity found in primary tumors. Yet, the genetic ancestral origin of cancer cell lines is rarely acknowledged and often unknown. Using genome-wide genotyping data from 1,393 cancer cell lines from the Catalogue of Somatic Mutations in Cancer (COSMIC) and Cancer Cell Line Encyclopedia (CCLE), we estimated the genetic ancestral origin for each cell line. Our data indicate that cancer cell line collections are not representative of the diverse ancestry and admixture characterizing human populations. We discuss the implications of genetic ancestry and diversity of cellular models for cancer research and present an interactive tool, Estimated Cell Line Ancestry (ECLA), where ancestry can be visualized with reference populations of the 1000 Genomes Project. Cancer researchers can use this resource to identify cell line models for their studies by taking ancestral origins into consideration.

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“…Genomic studies conducted in large AA and/or multi-ethnic cohorts have begun to utilize modified genomic tools in search of population-specific risk alleles. SNVs, structural, chromosomal, and epigenetic variations are being discovered and associated with a still theoretical genetic predisposition for the distinct tumor biology observed among women of West African descent (40)(41)(42)(43). While more risk alleles are being detected through increased diversity of multi-ethnic genome-wide association study (GWAS), the specific risk alleles transmitted into non-white populations through African genetic ancestry have not yet been definitively shown (44).…”

Section: Distinct Tumor Immune Responses Among Ancestry Groups With Cmentioning

confidence: 99%

Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry

Jenkins

Martini

Hire

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Tumor-specific immune response is an important aspect of disease prognosis and ultimately impacts treatment decisions for innovative immunotherapies. The atypical chemokine receptor 1 (ACKR1 or DARC) gene plays a pivotal role in immune regulation and harbors several singlenucleotide variants (SNV) that are specific to sub-Saharan African ancestry. Methods: Using computational The Cancer Genome Atlas (TCGA) analysis, case-control clinical cohort Luminex assays, and CIBERSORT deconvolution, we identified distinct immune cell profile-associated DARC/ACKR1 tumor expression and race with increased macrophage subtypes and regulatory T cells in DARC/ACKR1-high tumors. Results: In this study, we report the clinical relevance of DARC/ACKR1 tumor expression in breast cancer, in the context of a tumor immune response that may be associated with sub-Saharan African ancestry. Briefly, we found that for infiltrating carcinomas, African Americans have a higher proportion of DARC/ACKR1-negative tumors compared with white Americans, and DARC/ACKR1 tumor expression is correlated with proinflammatory chemokines, CCL2/MCP-1 (P <0.0001) and anticorrelated with CXCL8/IL8 (P <0.0001). Sub-Saharan African-specific DARC/ACKR1 alleles likely drive these correlations. Relapse-free survival (RFS) and overall survival (OS) were significantly longer in individuals with DARC/ACKR1-high tumors (P <1.0 Â 10 À16 and P <2.2 Â 10 À6 , respectively) across all molecular tumor subtypes. Conclusions: DARC/AKCR1 regulates immune responses in tumors, and its expression is associated with sub-Saharan African-specific alleles. DARC/ACKR1-positive tumors will have a distinct immune response compared with DARC/ AKCR1-negative tumors. Impact: This study has high relevance in cancer management, as we introduce a functional regulator of inflammatory chemokines that can determine an infiltrating tumor immune cell landscape that is distinct among patients of African ancestry.

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Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry

Cited by 44 publications

References 30 publications

Assessment of Intratumoral and Peritumoral Computed Tomography Radiomics for Predicting Pathological Complete Response to Neoadjuvant Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma

Assessment of Intratumoral and Peritumoral Computed Tomography Radiomics for Predicting Pathological Complete Response to Neoadjuvant Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma

An Interactive Resource to Probe Genetic Diversity and Estimated Ancestry in Cancer Cell Lines

Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry

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