Hereditary cancer predisposition gene testing allows the identification of individuals at high risk of cancer that may benefit from increased surveillance, chemoprevention, and prophylactic surgery. In order to implement clinical genetic strategies adapted to each population’s needs and intrinsic genetic characteristic, this review aims to present the current status of knowledge about the spectrum of BRCA pathogenic variants in Latin American populations. We have conducted a comprehensive review of 33 studies published between 1994 and 2015 reporting the prevalence and/or spectrum of BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variants. The combined sample size for these studies consisted of 4835 individuals from 13 countries in Latin America and the Caribbean, as well as in Hispanics in the United States. A total of 167 unique pathogenic variants have been reported in the existing literature. In unselected breast cancer cases, the prevalence ranged from 1.2 to 27.1 %. Some countries presented a few recurrent pathogenic variants, while others were characterized by diverse, non-recurrent variants. The proportion of BRCA pathogenic variants shared between Hispanics in the United States and Latin American populations was estimated at 10.4 %. Within Latin America and the Caribbean, 8.2 % of the BRCA variants reported were present in more than one country. Countries with high prevalence of BRCA pathogenic variants may benefit from more aggressive testing strategies, while testing of recurrent variant panels might present a cost-effective solution for improving genetic testing in some, but not all, countries.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3629-3) contains supplementary material, which is available to authorized users.

Studies have shown that DNA repair capacity is significantly decreased in breast cancer patients, but the molecular causes of inter-individual variations in DNA repair capacity are unknown. We hypothesized that genetic variations in the nucleotide excision repair pathway genes can modulate DNA repair capacity (DRC) and breast cancer risk in Puerto Rican women. A total of 228 breast cancer cases and 418 controls were recruited throughout Puerto Rico. For all study participants, eight SNPs in the genes XPC, XPD and RAD23B were genotyped using a TaqMan PCR, and the DRC levels of UV induced-DNA damage was measured in peripheral lymphocytes using a host cell reactivation assay. After adjustment for confounders, RAD23B rs1805329 (Ala249Val) was found to be significantly associated with breast cancer risk under all models tested (P<0.001). There was also a significant association between breast cancer risk and RAD23B rs10739234 (intronic) under the recessive model (P=0.003, OR: 2.72, 95% CI: 1.40–5.30). In cases, there was a statistically significant difference in mean DRC per genotype for RAD23B rs1805329 (P<0.001) and XPC rs2607775 (P=0.002). When we modeled the combined effect of multiple SNPs that each independently affected DRC on cancer risk, we observed incremental augmentations in risk with increasing number of risk genotypes at those loci (P overall model < 0.001). The increase in adverse genotypes was also correlated with a progressive decrease in DRC values. Our data indicate an additive effect of the NER SNPS on DRC and breast cancer risk in Puerto Rican women.

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