| Abstract | dc.description.abstract | 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 MTHFRT(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. | en_US |
