A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico
Breast cancer is the most common cause of cancer diagnosis in women and is responsible for considerable mortality among the women of Puerto Rico. However, there are few studies in Puerto Rico on the genetic factors influencing risk. To determine the contribution of pathogenic mutations in <i>B...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-11-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/10/11/419 |
id |
doaj-04ddb8fce3fc4187a2e90c1c5bc3443c |
---|---|
record_format |
Article |
spelling |
doaj-04ddb8fce3fc4187a2e90c1c5bc3443c2020-11-25T00:23:59ZengMDPI AGCancers2072-66942018-11-01101141910.3390/cancers10110419cancers10110419A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto RicoHector J. Diaz-Zabala0Ana P. Ortiz1Lisa Garland2Kristine Jones3Cynthia M. Perez4Edna Mora5Nelly Arroyo6Taras K. Oleksyk7Miguel Echenique8Jaime L. Matta9Michael Dean10Julie Dutil11Cancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Ponce, PR 00716-2348, USACancer Control and Population Sciences Program, Comprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936-5067, USACancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 21702, USACancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD 21702, USADepartment of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico, San Juan, PR 00936-5067, USADepartment of Surgery, School of Medicine, University of Puerto Rico and University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00936-5067, USACancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Ponce, PR 00716-2348, USABiology Department, Oakland University, Rochester, MI 48309-4454, USACancer Center, Auxilio Mutuo Hospital, San Juan, PR 00936-5067, USACancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Ponce, PR 00716-2348, USALaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD 20877, USACancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Ponce, PR 00716-2348, USABreast cancer is the most common cause of cancer diagnosis in women and is responsible for considerable mortality among the women of Puerto Rico. However, there are few studies in Puerto Rico on the genetic factors influencing risk. To determine the contribution of pathogenic mutations in <i>BRCA1</i> and <i>BRCA2</i>, we sequenced these genes in 302 cases from two separate medical centers, who were not selected for age of onset or family history. We identified nine cases that are carriers of pathogenic germline mutation. This represents 2.9% of unselected cases and 5.6% of women meeting National Comprehensive Cancer Network (NCCN) criteria for BRCA testing. All of the identified pathogenic mutations were in the <i>BRCA2</i> gene and the most common mutation is the p.Glu1308Ter (E1308X) mutation in <i>BRCA2</i> found in eight out of nine cases, representing 89% of the pathogenic carriers. The E1308X mutation has been identified in breast and ovarian cancer families in Spain, and analysis of flanking DNA polymorphisms shows that all E1308X carriers occur on the same haplotype. This is consistent with <i>BRCA2</i> E1308X being a founder mutation for the Puerto Rican population. These results will contribute to better inform genetic screening and counseling of breast and ovarian cancer cases in Puerto Rico and Puerto Rican populations in mainland United States.https://www.mdpi.com/2072-6694/10/11/419breast cancer genetics<i>BRCA1</i>/<i>BRCA2</i>founder effectHispanic and Latino populations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hector J. Diaz-Zabala Ana P. Ortiz Lisa Garland Kristine Jones Cynthia M. Perez Edna Mora Nelly Arroyo Taras K. Oleksyk Miguel Echenique Jaime L. Matta Michael Dean Julie Dutil |
spellingShingle |
Hector J. Diaz-Zabala Ana P. Ortiz Lisa Garland Kristine Jones Cynthia M. Perez Edna Mora Nelly Arroyo Taras K. Oleksyk Miguel Echenique Jaime L. Matta Michael Dean Julie Dutil A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico Cancers breast cancer genetics <i>BRCA1</i>/<i>BRCA2</i> founder effect Hispanic and Latino populations |
author_facet |
Hector J. Diaz-Zabala Ana P. Ortiz Lisa Garland Kristine Jones Cynthia M. Perez Edna Mora Nelly Arroyo Taras K. Oleksyk Miguel Echenique Jaime L. Matta Michael Dean Julie Dutil |
author_sort |
Hector J. Diaz-Zabala |
title |
A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico |
title_short |
A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico |
title_full |
A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico |
title_fullStr |
A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico |
title_full_unstemmed |
A Recurrent <i>BRCA2</i> Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico |
title_sort |
recurrent <i>brca2</i> mutation explains the majority of hereditary breast and ovarian cancer syndrome cases in puerto rico |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2018-11-01 |
description |
Breast cancer is the most common cause of cancer diagnosis in women and is responsible for considerable mortality among the women of Puerto Rico. However, there are few studies in Puerto Rico on the genetic factors influencing risk. To determine the contribution of pathogenic mutations in <i>BRCA1</i> and <i>BRCA2</i>, we sequenced these genes in 302 cases from two separate medical centers, who were not selected for age of onset or family history. We identified nine cases that are carriers of pathogenic germline mutation. This represents 2.9% of unselected cases and 5.6% of women meeting National Comprehensive Cancer Network (NCCN) criteria for BRCA testing. All of the identified pathogenic mutations were in the <i>BRCA2</i> gene and the most common mutation is the p.Glu1308Ter (E1308X) mutation in <i>BRCA2</i> found in eight out of nine cases, representing 89% of the pathogenic carriers. The E1308X mutation has been identified in breast and ovarian cancer families in Spain, and analysis of flanking DNA polymorphisms shows that all E1308X carriers occur on the same haplotype. This is consistent with <i>BRCA2</i> E1308X being a founder mutation for the Puerto Rican population. These results will contribute to better inform genetic screening and counseling of breast and ovarian cancer cases in Puerto Rico and Puerto Rican populations in mainland United States. |
topic |
breast cancer genetics <i>BRCA1</i>/<i>BRCA2</i> founder effect Hispanic and Latino populations |
url |
https://www.mdpi.com/2072-6694/10/11/419 |
work_keys_str_mv |
AT hectorjdiazzabala arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT anaportiz arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT lisagarland arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT kristinejones arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT cynthiamperez arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT ednamora arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT nellyarroyo arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT taraskoleksyk arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT miguelechenique arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT jaimelmatta arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT michaeldean arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT juliedutil arecurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT hectorjdiazzabala recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT anaportiz recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT lisagarland recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT kristinejones recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT cynthiamperez recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT ednamora recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT nellyarroyo recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT taraskoleksyk recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT miguelechenique recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT jaimelmatta recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT michaeldean recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico AT juliedutil recurrentibrca2imutationexplainsthemajorityofhereditarybreastandovariancancersyndromecasesinpuertorico |
_version_ |
1725354598509576192 |