Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range.

Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.

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Several recent pharmacogenetic studies have investigated the variability in both outcome and toxicity in cisplatin-based therapies. These studies have focused on the genetic variability of therapeutic targets that could affect cisplatin response and toxicity in diverse type of cancer including lung, gastric, ovarian, testicular, and esophageal cancer. In this review, we seek to update the reader in this area of investigation, focusing primarily on DNA reparation enzymes and cisplatin metabolism through Glutathione S-Transferases (GSTs). Current evidence indicates a potential application of pharmacogenetics in therapeutic schemes in which cisplatin is the cornerstone of these treatments. Therefore, a collaborative effort is required to study these molecular characteristics in order to generate a genetic panel with clinical utility.

Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of substantial efficacy and safety data on antithrombotic prophylaxis in several countries, particularly in Latin America. The aim of this study was to provide information about the efficacy of anticoagulants in Chilean patients. Data were collected from databases of the Western Metropolitan Health Service, Santiago, Chile. We identified 6280 records of patients receiving anticoagulant treatment. The three most common diagnoses were rhythm disorder (43.7%), venous thrombosis (22%), and valvular prosthesis (10.7%). The majority of patients (98.5%) received acenocoumarol while 1.5% of patients received warfarin, at weekly therapeutic doses of 13.6 mg and 30.4 mg, respectively. For total diagnoses, the median time in the therapeutic range was 50%. However, better results, 66.7%, were observed when a telemedicine strategy was used only in Santiago Province. Our findings emphasize that in Chile, where the number of patients receiving anticoagulant treatment increases every year, telemedicine, by committed teams, improves the use of oral anticoagulants and is able to increase quality indicators of anticoagulant treatment care.