A Recurrent BRCA2 Mutation Explains the Majority of Hereditary Breast and Ovarian Cancer Syndrome Cases in Puerto Rico

• Published in: Cancers Vol. 10; no. 11; p. 419
• Main Authors: Diaz-Zabala, Hector J, Ortiz, Ana P, Garland, Lisa, Jones, Kristine, Perez, Cynthia M, Mora, Edna, Arroyo, Nelly, Oleksyk, Taras K, Echenique, Miguel, Matta, Jaime L, Dean, Michael, Dutil, Julie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 02-11-2018
• Subjects: breast cancer genetics; Hispanic and Latino populations; founder effect; BRCA1/BRCA2
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers10110419

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
and
, 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
gene and the most common mutation is the p.Glu1308Ter (E1308X) mutation in
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
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.