Polymorphic variants of certain genes involved in gemcitabine metabolism and DNA damage repair pathways may be potential biomarkers for clinical outcome in patients with refractory/relapsed lymphoid tumors receiving gemcitabine/busulfann/melphalan (Gem/Bu/Mel). This according to a study of 21 germline single nucleotide polymorphisms (SNPs) of gemacitabine metabolism genes, damage repair genes, and multidrug resistance genes in 153 patients with relapsed or refractory lymphoma or myeloma receiving Gem/Bu/Mel. Researchers found:

• CDA C111T and TREX1 Ex14-460C>T genotypes had a significant effect on overall survival (OS).

• CDA C111T, ATR C340T and EXO1 P757L genotypes were significant predictors for severe toxicity in multivariable models that adjusted for clinical variables.

• Multi-SNP risk score analysis identified the combined genotypes of TREX1 Ex14-460 TT and hCNT3 Ex5 +25A>G AA as a significant predictor for OS and the combination of MRP2 Ex10 +40 GG/GA and MLH1 IVS12-169 TT as a significant predictor for progression-free survival.

Citation: Shinozuka K, Tang H, Jones RB, Li D, Nieto Y. Impact of polymorphic variations of gemcitabine metabolism, DNA damage repair, and drug resistance genes on the effect of high-dose chemotherapy for relapsed or refractory lymphoid malignancies. [Published online ahead of print December 29, 2015]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2015.12.022.