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.

Multi-gene hereditary cancer testing among men with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1532-1532
Author(s):  
Krystal Brown ◽  
Gregory Sampang Calip ◽  
Ryan Bernhisel ◽  
Brent Evans ◽  
Eric Thomas Rosenthal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Clinical Information ◽  
Gene Panel ◽  
Age At Diagnosis ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Personal Diagnosis

1532 Background: All men with a personal diagnosis of breast cancer (BC) are candidates for BRCA1/2 genetic testing, as pathogenic variants (PVs) in these genes have a known association with BC risk in both men and women. As additional genes with known BC risk in women are now routinely included in multi-gene panel testing, we evaluated the outcomes of multi-gene panel testing in a large cohort of men with BC. Methods: This analysis includes the results of commercial genetic testing for 1,358 men with BC usinga multi-gene pan-cancer panel between September 2013 and January 2017. Clinical information was obtained from provider-completed test request forms. Age at diagnosis, personal, and family history were compared for men with PVs in BRCA1/2 versus non- BRCA1/2 genes. Results: Overall, 207 (15.2%) men with BC were found to carry a PV, where 147 (10.8%) men had a PV in BRCA1/2 ( BRCA1, 0.7%; BRCA2, 10.2%) and 60 (4.4%) men had a PV in a non- BRCA1/2 gene ( CHEK2, 2.0%; ATM, 1.0%; PALB2, 1.0%; BARD1, 0.2%; NBN, 0.2%; MSH6, 0.1%; BRIP1, 0.1%; CDH1, 0.1%; CDKN2A, 0.1%; MLH1, 0.1%, TP53, 0.1%). There were no substantial differences in the median age-at-diagnosis for men without a PV (65) compared to those with a BRCA1/2 PV (66) or a non- BRCA1/2 PV (63). Prostate cancer was the most common additional malignancy among all men with BC (9.0%), with a similar incidence among men with a BRCA1/2 PV (9.2%) and a non- BRCA1/2 PV (8.3%). In addition, 1.4% of men with a BRCA1/2 PV and 3.3% of men with a non- BRCA1/2 PV had a second BC. A family history of breast and/or ovarian cancer was present in 44.4% of the testing cohort, 66.7% of men with a BRCA1/2 PV, and 48.3% of men with a non- BRCA1/2 PV. This is consistent with the relative penetrance of BRCA1/2 and other genes included here. There were no other substantial differences in family history among BRCA1/2 PV carriers versus non- BRCA1/2 PV carriers. Conclusions: Close to a third of all PVs identified here in men with BC were in a gene other than BRCA1/2. There were no obvious differences in the clinical presentation of men with a BRCA1/2 PV compared to men with a PV in another gene or no PV at all. Collectively, this suggests that multi-gene panel testing is appropriate for all men with BC, regardless of other personal or family history.

scholarly journals Germline Mutations in a Clinic-based Series of Pregnancy Associated Breast Cancer Patients

2021 ◽  
Author(s):  
Eleni Zografos ◽  
Anna-Maria Korakiti ◽  
Angeliki Andrikopoulou ◽  
Ioannis Rellias ◽  
Constantine Dimitrakakis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Genetic Predisposition ◽  
Cancer Susceptibility ◽  
Germline Mutations ◽  
Susceptibility Genes ◽  
Management Approach ◽  
Breast Cancer Patients ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes

Abstract Background: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within one year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC.Methods: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients’ clinicopathological data. Results: In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer.Conclusions: Genetic testing should be offered to PABC patients regardless of family history as the disease is highly associated with genetic predisposition. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.

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