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

Megan Ren; Anali Orozco; Kang Shao; Anaseidy Albanez; Jeremy Ortiz; Boyang Cao; Lusheng Wang; Lilian Barreda; Christian S. Alvarez; Lisa Garland; Dongjing Wu; Charles C. Chung; Jiahui Wang; Megan Frone; Sergio Ralon; Victor Argueta; Roberto Orozco; Eduardo Gharzouzi; Michael Dean

doi:10.1007/s10549-021-06305-5

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

Megan Ren (Co-first Author)
, Anali Orozco (Co-first Author)
, Kang Shao (Co-first Author)
, Anaseidy Albanez
, Jeremy Ortiz
, Boyang Cao
, Lusheng Wang
, Lilian Barreda
, Christian S. Alvarez
, Lisa Garland
, Dongjing Wu
, Charles C. Chung
, Jiahui Wang
, Megan Frone
, Sergio Ralon
, Victor Argueta
, Roberto Orozco^*
, Eduardo Gharzouzi^*
, Michael Dean^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

9 Citations (Scopus)

55 Downloads (CityUHK Scholars)

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.

Original language	English
Journal	Breast Cancer Research and Treatment
Volume	189
Issue number	2
Online published	1 Jul 2021
DOIs	https://doi.org/10.1007/s10549-021-06305-5
Publication status	Published - Sept 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

Research Keywords

BRCA1 gene
BRCA2 gene
Health disparities
Hispanic
Latin America
Pathogenic mutation

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

RGC Funding Information

RGC-funded

Access Output

10.1007/s10549-021-06305-5

79450605.pdfFinal Published version, 626 KBLicence: CC BY

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

Ren, M., Orozco, A., Shao, K., Albanez, A., Ortiz, J., Cao, B., Wang, L., Barreda, L., Alvarez, C. S., Garland, L., Wu, D., Chung, C. C., Wang, J., Frone, M., Ralon, S., Argueta, V., Orozco, R., Gharzouzi, E., & Dean, M. (2021). Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer. Breast Cancer Research and Treatment, 189(2). https://doi.org/10.1007/s10549-021-06305-5

@article{d5d5c9f12fc040bf9154985905be2243,

title = "Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer",

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.",

keywords = "BRCA1 gene, BRCA2 gene, Health disparities, Hispanic, Latin America, Pathogenic mutation",

author = "Megan Ren and Anali Orozco and Kang Shao and Anaseidy Albanez and Jeremy Ortiz and Boyang Cao and Lusheng Wang and Lilian Barreda and Alvarez, \{Christian S.\} and Lisa Garland and Dongjing Wu and Chung, \{Charles C.\} and Jiahui Wang and Megan Frone and Sergio Ralon and Victor Argueta and Roberto Orozco and Eduardo Gharzouzi and Michael Dean",

year = "2021",

month = sep,

doi = "10.1007/s10549-021-06305-5",

language = "English",

volume = "189",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "2",

}

Ren, M, Orozco, A, Shao, K, Albanez, A, Ortiz, J, Cao, B, Wang, L, Barreda, L, Alvarez, CS, Garland, L, Wu, D, Chung, CC, Wang, J, Frone, M, Ralon, S, Argueta, V, Orozco, R, Gharzouzi, E & Dean, M 2021, 'Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer', Breast Cancer Research and Treatment, vol. 189, no. 2. https://doi.org/10.1007/s10549-021-06305-5

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer. / Ren, Megan (Co-first Author); Orozco, Anali (Co-first Author); Shao, Kang (Co-first Author) et al.
In: Breast Cancer Research and Treatment, Vol. 189, No. 2, 09.2021.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

AU - Ren, Megan

AU - Orozco, Anali

AU - Shao, Kang

AU - Albanez, Anaseidy

AU - Ortiz, Jeremy

AU - Cao, Boyang

AU - Wang, Lusheng

AU - Barreda, Lilian

AU - Alvarez, Christian S.

AU - Garland, Lisa

AU - Wu, Dongjing

AU - Chung, Charles C.

AU - Wang, Jiahui

AU - Frone, Megan

AU - Ralon, Sergio

AU - Argueta, Victor

AU - Orozco, Roberto

AU - Gharzouzi, Eduardo

AU - Dean, Michael

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - BRCA1 gene

KW - BRCA2 gene

KW - Health disparities

KW - Hispanic

KW - Latin America

KW - Pathogenic mutation

UR - https://www.scopus.com/pages/publications/85109075197

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85109075197&origin=recordpage

U2 - 10.1007/s10549-021-06305-5

DO - 10.1007/s10549-021-06305-5

M3 - RGC 21 - Publication in refereed journal

C2 - 34196900

SN - 0167-6806

VL - 189

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 2

ER -

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

Abstract

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

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

GRF: Algorithms for Searching MS Spectra against Protein Databases and Protein Sequencing Using Combined Top-down and Bottom-up Approach for Monoclonal Antibodies

GRF: Efficient Algorithms for Identification of Modified Proteoforms Using Top-down Mass Spectra

Cite this

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

Abstract

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Research output

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

Projects

GRF: Algorithms for Searching MS Spectra against Protein Databases and Protein Sequencing Using Combined Top-down and Bottom-up Approach for Monoclonal Antibodies

GRF: Efficient Algorithms for Identification of Modified Proteoforms Using Top-down Mass Spectra

Cite this