ABSTRACT
Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.
ABSTRACT
PURPOSE: Ubiquitin ligase genes can act as oncogenes or tumor suppressor genes. They play a role in various diseases, including development and progression of breast cancer; the objective of this study was to evaluate the association of common variants in the ductal-epithelium-associated RING chromosome 1 (DEAR1) gene with breast cancer risk in a sample of Colombian population. METHODS: We carried out a case-control study to investigate associations of variants in DEAR1 with breast cancer in women from Colombia. Single nucleotide polymorphisms (SNPs) rs584298, rs2927970, rs59983645, and rs599167 were genotyped in 1022 breast cancer cases and 1023 healthy controls using the iPLEX® and Kompetitive Allele Specific PCR (polymerase chain reaction) (KASP) method. The associations between SNPs and breast cancer were examined by conditional logistic regression. The associations between SNPs and epidemiological/histopathological variables were examined by multinomial logistic regression. RESULTS: Associations were found between tag SNPs and breast cancer adjusted for the epidemiological risk factors rs584298 genotypes AG and GG (P = .048 and P = .004, respectively). The analysis of the disease characteristics showed that SNP rs584298 (genotype AG) (P = .015) shows association with progesterone receptor (PR) status and (genotype AA) (P = .048) shows association with human epidermal growth factor receptor 2 (HER2) status. CONCLUSIONS: The SNP rs584298 in DEAR1 showed associations with breast cancer and the expression of HER2 receptor; when this receptor is amplified, the result is aggressive tumoral subtype and expression of PR receptor that is associated with high-proliferative tumor grade. Validation of this SNP is important to establish whether this variant or the tagged variant is the cause for the risk association showed.
