कार्सिनोजेनेसिस और उत्परिवर्तन जर्नल

अमूर्त

Common BRCA1 and BRCA2 Mutations among Latin American Breast Cancer Subjects: A Meta-Analysis

Leonardo M Porchia, M Elba González Mejia, Luis Calderilla-Barbosa, Nirvana I Ordaz Diaz, Fabiola Islas Lugo, José Oldak, Rossana C Zepeda and Gisela Aguirre

Background: Many BRCA1 and BRCA2 mutations have been characterized in breast cancer subjects; however, the overall prevalence in Latin American remains elusive. The aim of the study was to determine the prevalence of common BRCA1 and BRCA2 mutations in Latin American breast cancer subjects.

Methods: Pubmed, EBSCO, and OVID databases, and study bibliographies were systematically searched for observational studies that examined for mutations in BRCA1 and BRCA2 until March 2015. The pooled prevalence was obtained using the inverse double arcsine square root method. Publication bias was assessed by Begg and Mazumdar’s test and the Egger’s test. The sensitivity was determined by reevaluation of the pooled estimate after removal of one study.

Results: Out of 294 retrieved studies, 32 studies met the inclusion criteria (n=9938 subjects). Twenty-nine BRCA1 and thirteen BRCA2 pathogenic mutations were described in two or more studies. For BRCA1, the most reported mutations were 185delAG and A1708E. The most prevalent BRCA1 mutations (>0.50%) were del exon 9–12 (1.45%, 95% CI: 0.61–2.63%), 185delAG (0.90%, 95% CI: 0.50–1.42%), R71G (0.64%, 95% CI: 0.43–0.87%), A1708E (0.58%, 95% CI: 0.40–0.79%), 5382insC (0.54%, 95% CI: 0.32–0.82%), and del exon 16–17 (0.54%, 95% CI: 0.32–0.82%). For BRCA2, the most reported mutations were 6174delT and 3036del4; however, the H372N (0.78%, 95% CI: 0.14–1.82%) was the most frequent (>0.50%). Comparing Mexican-based studies to the remaining Latin American reports, we provide evidence that certain mutations are specific only for Mexicans and their descendants (i.e. BRCA1 del exon 9–12 and BRCA2 3492insT, G273R, and W2586X).

Conclusion: Here we identify the most common BRCA1 and BRCA2 mutations among Latin Americans. This information will aid in selecting mutations for genetic testing and in epidemiological studies.