TY - JOUR
T1 - Genetic polymorphisms predicting methotrexate blood levels and toxicity in adult non-Hodgkin lymphoma
AU - Avivi, Irit
AU - Zuckerman, Tsila
AU - Krivoy, Norberto
AU - Efrati, Edna
PY - 2014/3
Y1 - 2014/3
N2 - Methotrexate (MTX), a folate antagonist employed for treating a wide range of malignancies, has an extensive interpatient variability, resulting in unpredictable toxicity. The present study evaluated the impact of single gene polymorphisms (SNPs: rs1801133 and rs1801131 in the MTHFR gene; rs4149056 and rs11045879 in the SLC01B1 gene; and rs2032582 and rs1045642 in the ABCB1 transporter gene) on MTX blood levels and toxicity in samples from 69 patients with diffuse large-B-cell lymphoma (DLBCL) treated with high dose intravenous (HD IV) MTX, > 2 g/m. None of the studied genotypes was found to be associated with a statistically significant risk for elevated MTX levels at 24-48 h after completing therapy with MTX. Ancestral alleles (T) for SLC01B1 rs4149056 (T521C) and SLC01B1 rs11045879 (intron C21273886T) were found to be associated with an increased risk for MTX-related toxicity (p < 0.05 and p = 0.07, respectively), emphasizing the potential importance of employing pharmacogenetic assessment for personalized medicine.
AB - Methotrexate (MTX), a folate antagonist employed for treating a wide range of malignancies, has an extensive interpatient variability, resulting in unpredictable toxicity. The present study evaluated the impact of single gene polymorphisms (SNPs: rs1801133 and rs1801131 in the MTHFR gene; rs4149056 and rs11045879 in the SLC01B1 gene; and rs2032582 and rs1045642 in the ABCB1 transporter gene) on MTX blood levels and toxicity in samples from 69 patients with diffuse large-B-cell lymphoma (DLBCL) treated with high dose intravenous (HD IV) MTX, > 2 g/m. None of the studied genotypes was found to be associated with a statistically significant risk for elevated MTX levels at 24-48 h after completing therapy with MTX. Ancestral alleles (T) for SLC01B1 rs4149056 (T521C) and SLC01B1 rs11045879 (intron C21273886T) were found to be associated with an increased risk for MTX-related toxicity (p < 0.05 and p = 0.07, respectively), emphasizing the potential importance of employing pharmacogenetic assessment for personalized medicine.
KW - Adult non-Hodgkin lymphoma
KW - Gene polymorphisms
KW - Methotrexate toxicity
KW - Prediction
UR - http://www.scopus.com/inward/record.url?scp=84894482124&partnerID=8YFLogxK
U2 - 10.3109/10428194.2013.789506
DO - 10.3109/10428194.2013.789506
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C2 - 23829278
AN - SCOPUS:84894482124
SN - 1042-8194
VL - 55
SP - 565
EP - 570
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -
