scholarly journals Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women

2017 ◽  
Vol 27 (2) ◽  
pp. 169 ◽  
Author(s):  
Luisel Ricks-Santi ◽  
J. Tyson McDonald ◽  
Bert Gold ◽  
Michael Dean ◽  
Nicole Thompson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Next Generation Sequencing ◽  
Family History ◽  
African American Women ◽  
Additive Model ◽  
Age At Diagnosis ◽  
History Of ◽  
Generation Sequencing

<p class="Pa7"><strong>Background: </strong>Variants of unknown signifi­cance (VUSs) have been identified in <em>BRCA1 </em>and <em>BRCA2 </em>and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age.</p><p class="Pa7"><strong>Methods: </strong>In our study, the spectrum of mu­tations in <em>BRCA1 </em>and <em>BRCA2 </em>was enumer­ated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the <em>BRCA1 </em>and <em>BRCA2 </em>variants, bioinfor­matics tools were utilized to predict the potential function of each of the variants.</p><p class="Pa7"><strong>Results: </strong>Using next generation sequencing methods and <em>in silico </em>analysis of variants, a total of 197 <em>BRCA1 </em>and 266 <em>BRCA2 </em>vari­ants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; <em>BRCA2 </em>Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemio­logical approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14).</p><p class="Pa7"><strong>Conclusions: </strong>Knowing a patient’s BRCA mutation status is important for prevention and treatment decision-making. Improv­ing the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Ameri­cans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies. <em></em></p><p class="Pa7"><em>Ethn Dis. </em>2017;27(1):169-178; doi:10.18865/ed.27.2.169</p>

The Impact of a Family History of Breast Cancer on Screening Practices and Attitudes in Low-Income, Rural, African American Women

2003 ◽  
Vol 12 (8) ◽  
pp. 779-787 ◽  
Author(s):  
Delia Smith West ◽  
Paul G. Greene ◽  
Polly P. Kratt ◽  
Leavonne Pulley ◽  
Heidi L. Weiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
African American Women ◽  
Low Income ◽  
American Women ◽  
Screening Practices ◽  
History Of ◽  
The Impact

scholarly journals Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

2015 ◽  
Vol 25 (2) ◽  
pp. 366-373 ◽  
Author(s):  
Traci N. Bethea ◽  
Lynn Rosenberg ◽  
Nelsy Castro-Webb ◽  
Kathryn L. Lunetta ◽  
Lara E. Sucheston-Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
African American Women ◽  
Breast Cancer Subtypes ◽  
American Women ◽  
Cancer Subtypes ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next-generation sequencing.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. CRA1501-CRA1501 ◽  
Author(s):  
Jane E. Churpek ◽  
Tom Walsh ◽  
Yonglan Zheng ◽  
Silvia Casadei ◽  
Anne M. Thornton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Next Generation Sequencing ◽  
Family History ◽  
Cancer Patients ◽  
Cancer Genes ◽  
Breast Cancer Patients ◽  
Inherited Mutations ◽  
Generation Sequencing ◽  
Breast Cancer Genes

CRA1501 Background: African American (AA) women are disproportionately affected by early-onset and triple-negative breast cancer (TNBC). One explanation for these disparities may be a higher frequency of inherited mutations among AA women in genes in DNA repair pathways, including BRCA1 and BRCA2. Using targeted genomic capture and next generation sequencing (NGS), we screened DNA from AA women with breast cancer for mutations in all 18 known breast cancer genes. Methods: A total of 249 unrelated AA women with breast cancer were ascertained through the Cancer Risk Clinic at The University of Chicago. Genomic DNA was extracted from peripheral blood and 3 micrograms were used for targeted capture and sequencing. Average read depth across the 1.4 MB targeted region was 320-fold. Sequence reads were aligned and all classes of variants identified: point mutations, small insertions and deletions, and large genomic rearrangements. Only unambiguously damaging mutations were called: stops, complete genomic deletions, and missenses demonstrated experimentally to cause loss of protein function. Variants were validated by PCR or Taqman analysis. Results: Fifty-six of 249 subjects (22%) carried at least one loss-of-function mutation, distributed among BRCA1 (n=26), BRCA2 (n=20), CHEK2 (n=3), PALB2 (n=3), ATM (n=5), and PTEN (n=1). The majority of mutations were unique. Damaging mutations were carried by 30% of patients with TNBC, 27% of patients diagnosed at age ≤45, 49% with a second breast primary, and 30% with a family history of either breast or ovarian cancer in any close relative. Conclusions: We present the first comprehensive screen of all known breast cancer susceptibility genes among AA women using NGS. Mutation carrier frequencies are >25% for major subsets of patients defined by tumor or host characteristics. These high carrier frequencies suggest the importance of screening for mutations in all breast cancer genes in all AA breast cancer patients diagnosed at a young age, with a family history, or with TNBC as a way to identify at-risk family members for life-saving interventions.

Breast cancer screening behaviors among African American women with a strong family history of breast cancer

2006 ◽  
Vol 43 (5) ◽  
pp. 385-388 ◽  
Author(s):  
Chanita Hughes Halbert ◽  
Lisa Kessler ◽  
E. Paul Wileyto ◽  
Benita Weathers ◽  
Jill Stopfer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Cancer Screening ◽  
Family History ◽  
African American Women ◽  
Breast Cancer Screening ◽  
Strong Family History ◽  
American Women ◽  
History Of ◽  
Screening Behaviors

Germline mutation rate in African-American women in Arkansas with a personal and/or family history of breast cancer

2018 ◽  
Vol 149 ◽  
pp. 225-226
Author(s):  
K.K. Zorn ◽  
M.E. Simonson ◽  
A. Compadre ◽  
K.E. Gray ◽  
G.A. Runnells ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
African American Women ◽  
Mutation Rate ◽  
Germline Mutation ◽  
American Women ◽  
History Of

Breast Cancer Risk Estimates for Relatives of White and African American Women With Breast Cancer in the Women's Contraceptive and Reproductive Experiences Study

2006 ◽  
Vol 24 (16) ◽  
pp. 2498-2504 ◽  
Author(s):  
Michael S. Simon ◽  
Jeannette F. Korczak ◽  
Cecilia L. Yee ◽  
Kathleen E. Malone ◽  
Giske Ursin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
African American Women ◽  
White Women ◽  
Cancer Risks ◽  
Risk Estimates ◽  
History Of

Purpose Family history is a well-recognized risk factor for breast cancer. Familial aggregation and segregation analyses have estimated breast cancer risk based on family history primarily for white women; such information is limited for African American (AA) women. The purpose of this report is to update breast cancer risk estimates associated with a family history of breast cancer for white and AA women. Methods We used family cancer history from 2,676 white and 1,525 AA women with breast cancer (probands) in the population-based National Institute of Child Health and Human Development's Women's Contraceptive and Reproductive Experiences (CARE) Study to estimate age-specific breast cancer risks in their first degree adult female relatives. Cumulative hazard curves were calculated for relatives of all probands using Cox proportional hazards models, and were stratified by the proband's race and age at diagnosis and number of relatives affected. Results Breast cancer risks for white and AA women with a family history of the disease are similar through age 49 years, but diverge afterwards, with higher risks by age 79 in white women than in AA women (17.5% [SE, 0.9%] v 12.2% [SE, 1.1%]; P < .001). These risks increase as the number of affected first degree relatives increases, reaching 25.2% (SE, 3.4%) and 16.9% (SE, 4.0%) in white and AA women with more than one affected relative, respectively (P = .3). Conclusion We found age-related racial differences in breast cancer risk in women with a family history of breast cancer and have updated risk estimates for white and AA women for clinical use.

IL-6 and Soluble Receptors in Overweight and Obese African American Women With and Without Breast Cancer

2020 ◽  
pp. 109980042094578
Author(s):  
K. A. Griffith ◽  
A. S. Ryan
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
African American ◽  
African American Women ◽  
Strong Correlation ◽  
High Serum ◽  
Phenotypic Data ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
History Of

Interleukin 6 (IL-6) and its receptors are expressed in approximately half of breast cancer (BC) tissues, and high serum IL-6 levels are associated with poor prognosis. African American (AA) patients with BC have higher serum IL-6 levels compared to Caucasians, suggesting additional risk of disease-related complications in AAs. The purpose of this study was to compare IL-6 complex biomarkers in AA women with and without a history of BC.  We conducted a secondary analysis of phenotypic data from two studies of weight loss in AA women with and without a history of BC who had similar age and adiposity. Biomarkers analyzed included tumor necrosis factor alpha (TNF-α), IL-6, IL-6 soluble receptor (IL6sr), and soluble glycoprotein 130 (GP130); IL6sr and GP130 were newly analyzed for this study.  TNF-α levels were 1.86 times higher in the BC group (N = 7) compared to those without BC (N = 10; p < 0.001) despite similar age, weight, and body mass index. GP130 levels tended to be higher in women with BC; IL-6 and Il-6 sr were not different between groups. There was a strong correlation between GP130 and TNF-α (r = .638; p = .006) in the group overall.  High TNF-α levels in the BC group and a strong correlation between GP130 and TNF-α in the overall group suggest the presence of IL-6 complex initiated TNF-α production. Further study is needed to evaluate IL-6 reduction through a variety of approaches, including weight loss and anti-IL-6 therapies, which may ultimately implicate the reduction of IL-6 complex associated BC-specific recurrence and mortality.

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