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Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon
Ist Teil von
Cancer chemotherapy and pharmacology, 2021-11, Vol.88 (5), p.837-844
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2021
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose
Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon.
Methods
The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs).
Results
The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of
FPGS
(
p
= 0.001; OR 3.40; CI 95% 1.65–7.00 and
p
= 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of
ABCC4
(
p
= 0.023; OR 2.74; CI 95% 1.14–6.65 and
p
= 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the
SLC29A1
gene (
p
= 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the
MTHFR
toxicity (
p
= 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction.
Conclusion
Four polymorphisms of the
ABCC4
,
FPGS
,
SLC29A1,
and
MTHFR
genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.