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.

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 Gene Mutations in Hereditary Breast Cancer- A Review

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Pathima Fairoosa ◽  
Chamindri Witharana
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Gene Mutations ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Germline Gene ◽  
Brca1 And Brca2 ◽  
Repair Gene ◽  
Cancer Susceptibility Genes

The most prevalent form of cancer in females is breast cancer. Roughly 5%-10% of breast cancers are hereditary, and they are associated with Germline gene mutations, inherited from parents. Germline gene mutations increase the risk of developing cancer earlier in life compared to noninherited cases (sporadic cancer). BRCA1 and BRCA2 are well-studied tumour suppressor genes associated with hereditary breast cancer. Even though mutations in BRCA1 and BRCA2 are assumed to responsible the majority of hereditary breast cancers cases, many other breast cancer susceptibility genes have been identified in the last few decades. Identification of many germline mutations was possible due to advance sequencing technologies. Most of these genes are belongs to tumour suppressors and DNA damage repair gene families (DNA double-strand break repair and DNA mismatch repair). These genes play a vital role in genomic stability and cell cycle control suggesting that any alteration in these genes trigger uncontrolled growth and tumour formation. These genes are categorized according to the penetrance level, the proportion of carriers express the associated trait of the mutated gene. Mutations in high penetrance genes such as BRCA1, BRCA2, TP53, PTEN, and SKT11 greatly increase the risk of developing breast cancer. Moderate penetrance gene such as PALB2, ATM, CHEK2, BARD1, BRIP1 and low penetrance gene such as PARP4, CASP8, TOX3 confer moderate to low increase risk of developing breast cancer. Aim of this review is to summarize genes associated with hereditary breast cancer according to their penetrance level (high, moderate and low penetrance).

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
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