Interaction between BCL2 and interleukin-10 gene polymorphisms alter outcomes of diffuse large B-cell lymphoma following rituximab plus CHOP chemotherapy

Abstract

Purpose: Rituximab may overcome bcl-2-mediated chemoresistance through the inhibition of interleukin-10 (IL-10)-mediated loops, thus down-regulating bcl-2 expression. We examined the effects of genetic variation in BCL2//L10 gene loops on treatment outcomes of diffuse large B-cell lymphoma when treated with either CHOP or rituximab plus CHOP (R-CHOP) chemotherapy. Experimental Design: Four genotypes were tested including BCL2-938 C>A(rs2279115), +21 A>G (rs1801018), IL10-819 T>C (rs1800871), and-592 A>C (rs1800872) in patients receiving either R-CHOP (n = 125) or CHOP (n = 110). Results: IL10 SNPs,-819 TT/TC or-592 AA/AC genotypes correlated with improved CHOP response rates (P = 0.04). Neither polymorphism separately influenced the failure-free survival (FFS) or overall survival in patients, but the IL10 haplotype was associated with treatment outcomes after R-CHOP for FFS (P = 0.03) or progression (P = 0.007), whereas the-938 AA BCL2 genotype significantly affected overall survival (P = 0.04). An interactive effect between BCL2 and IL10 SNPs was significant in the group with both-938 AA BCL2 genotype and 1 to 2 copies of CC IL10 haplotype. This group showed a better FFS (P = 0.01) and a lower probability of progression (P = 0.004) compared with other genotype groups when treated with R-CHOP chemotherapy. Conclusions: These data indicated that R-CHOP chemotherapy resistance in diffuse large B-cell lymphoma may involve interactions between the BCL2 and IL10 genes.© 2009 American Association for Cancer Research.