scholarly journals Correction to: Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

2021 ◽  
Author(s):  
Megan Ren ◽  
Anali Orozco ◽  
Kang Shao ◽  
Anaseidy Albanez ◽  
Jeremy Ortiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Hereditary Breast Cancer ◽  
Age At Diagnosis ◽  
Early Age ◽  
Cancer Genes ◽  
Germline Variants ◽  
Breast Cancer Genes

scholarly journals Germline mutations in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

2020 ◽  
Author(s):  
Megan Ren ◽  
Anali Orozco ◽  
Kang Shao ◽  
Boyang Cao ◽  
Lusheng Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Hereditary Breast Cancer ◽  
Breast Cancer Mortality ◽  
Age At Diagnosis ◽  
Early Age ◽  
Cancer Genes ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Genes

Background: Mutations in hereditary breast cancer genes play an important role in the risk for cancer, however, little is known of the type and frequency of mutations in Central American populations, including Guatemala. Methods: Two separate panels of known cancer susceptibility genes were used to sequence blood DNA from 664 unselected breast cancer cases from two large hospitals in Guatemala. Variants were annotated with ClinVar and VarSome. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes. Results: A total of 73 out of 664 subjects (11%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%) and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212+1G>A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P<0.001), more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P=0.038) or breast cancer (33% vs 15%, P<0.001). Mammography usage was less frequent in lower SES women indicating this group is less likely to be screened for breast cancer (p < 0.001). Conclusions: Guatemalan women have rates of hereditary breast cancer mutations similar to other populations, and these women are more likely to have early age at diagnosis and family history. This data supports the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

scholarly journals Germline mutations in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

2020 ◽  
Author(s):  
Megan Ren ◽  
Anali Orozco ◽  
Kang Shao ◽  
Anaseidy Albanez ◽  
Jeremy Ortiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Hereditary Breast Cancer ◽  
Breast Cancer Mortality ◽  
Age At Diagnosis ◽  
Early Age ◽  
Cancer Genes ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Genes

Abstract Background: Mutations in hereditary breast cancer genes play an important role in the risk for cancer, however, little is known of the type and frequency of mutations in Central American populations, including Guatemala.Methods: Two separate panels of known cancer susceptibility genes were used to sequence blood DNA from 664 unselected breast cancer cases from two large hospitals in Guatemala. Variants were annotated with ClinVar and VarSome. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes.Results: A total of 73 out of 664 subjects (11%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%) and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). Mammography usage was less frequent in lower SES women indicating this group is less likely to be screened for breast cancer (p < 0.001).Conclusions: Guatemalan women have rates of hereditary breast cancer mutations similar to other populations, and these women are more likely to have early age at diagnosis and family history. This data supports the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

scholarly journals Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

2021 ◽  
Author(s):  
Megan Ren ◽  
Anali Orozco ◽  
Kang Shao ◽  
Anaseidy Albanez ◽  
Jeremy Ortiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Mortality ◽  
Age At Diagnosis ◽  
Early Age ◽  
Cancer Genes ◽  
Cancer Susceptibility Genes ◽  
Breast Cancer Genes

Abstract Purpose Mutations in hereditary breast cancer genes play an important role in the risk for cancer. Methods Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. Results A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). Conclusions Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

Hereditary Breast Cancer Genes

Breast Cancer ◽  
2003 ◽  
pp. 199-224
Author(s):  
Lynda B. Bennett ◽  
Joel D. Taurog ◽  
Anne M. Bowcock
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Genes ◽  
Breast Cancer Genes

Hereditary Breast Cancer Genes

Breast Cancer ◽  
1999 ◽  
pp. 199-224 ◽  
Author(s):  
Lynda B. Bennett ◽  
Joel D. Taurog ◽  
Anne M. Bowcock
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Genes ◽  
Breast Cancer Genes

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.

scholarly journals Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
T. Pesaran ◽  
R. Karam ◽  
R. Huether ◽  
S. Li ◽  
S. Farber-Katz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bioinformatics Analysis ◽  
Integrated Approach ◽  
Cancer Genes ◽  
Germline Variants ◽  
New Era ◽  
Functional Assays ◽  
Individualized Care ◽  
Variant Assessment ◽  
Breast Cancer Genes

Genetic testing for hereditary breast cancer is an integral part of individualized care in the new era of precision medicine. The accuracy of an assay is reliant on not only the technology and bioinformatics analysis utilized but also the experience and infrastructure required to correctly classify genetic variants as disease-causing. Interpreting the clinical significance of germline variants identified by hereditary cancer testing is complex and has a significant impact on the management of patients who are at increased cancer risk. In this review we give an overview of our clinical laboratory’s integrated approach to variant assessment. We discuss some of the nuances that should be considered in the assessment of genomic variants. In addition, we highlight lines of evidence such as functional assays and structural analysis that can be useful in the assessment of rare and complex variants.

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