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Genotype Can Figure in Cancer Prognosis and Treatment

Studies explore role of genotype in AML prognosis and drug dosage tolerance in CRC

MONDAY, Jan. 4 (HealthDay News) -- A patient's genotype can affect their prognosis in certain cancers, as well as their medication tolerance, and should be taken into account in evaluation and treatment, according to a pair of studies published online Dec. 28 in the Journal of Clinical Oncology.

Frederik Damm, M.D., of Hannover Medical School in Germany, and colleagues sequenced genes in 249 patients with cytogenetically normal acute myeloid leukemia (CN-AML) and 50 healthy subjects with a focus on the WT1 exons 7 and 9 and the NPM1, FLT3, CEBPA, and MLL genes. The minor allele of single nucleotide polymorphism rs16754 found in 25.7 percent of the CN-AML patients was found to be an independent predictor of relapse-free survival.

In another study, Giuseppe Toffoli, M.D., of the Centro di Riferimento Oncologico National Cancer Institute in Aviano, Italy, and colleagues enrolled 59 patients with colorectal cancer treated with irinotecan plus fluorouracil/leucovorin (FOLFIRI) with either the *1/*1 or the *1/*28 genotype. Irinotecan doses were increased from 215 mg/m2 to 370 mg/m2 in subjects with the *1/*28 genotype, and to 420 mg/m2 in those with the *1/*1 genotype (fluorouracil dosage remained constant). The researchers found that toxicities occurred in two subjects in the *1/*28 group at 370 mg/m2 but not in 10 others, and there were toxicities in two *1/*1 patients at 420 mg/m2 but not in 10 others.

"The recommended dose of 180 mg/m2 for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated when patients with the UGT1A1 *28/*28 genotype are excluded. Prospective genotype-driven studies should test the efficacy of higher irinotecan doses in the FOLFIRI schedule," Toffoli and colleagues conclude.

Abstract - Damm
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Abstract - Toffoli
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