BACKGROUND:
This
study aimed to determine whether single nucleotide polymorphisms (SNPs)
in genes involved in DNA repair or metabolism of taxanes or platinum
could predict toxicity or response to first-line chemotherapy in ovarian
cancer.
METHODS:
Twenty-six
selected SNPs in 18 genes were genotyped in 322 patients treated with
first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes
were correlated with toxicity events (anemia, neutropenia,
thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth
factors and survival.
RESULTS:
The
risk of anemia was increased for variant alleles of rs1128503 (ABCB1,
C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1,
A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1,
T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was
decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004,
OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of
thrombocytopenia was associated with rs4986910 (CYP3A4, T > C;
p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations
were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2,
A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1,
A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2,
G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the
use of colony stimulating factors (CSF), while rs2074087 (ABCC1,
G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of
erythropoiesis stimulating agents (ESAs). Homozygous carriers of the
rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free
interval (p = 0.016).
CONCLUSIONS:
Our
data reveal significant correlations between genetic variants of
transport, hepatic metabolism, platinum related detoxification or DNA
damage repair and toxicity or outcome in ovarian cancer.
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