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Interaction between BCL2 and Interleukin-10 Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy

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Affiliated Author(s)
송홍석
Alternative Author(s)
Song, Hong Suk
Journal Title
Clinical Cancer Research
ISSN
1078-0432
Issued Date
2009
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/IL10 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.
Department
Dept. of Internal Medicine (내과학)
Publisher
School of Medicine
Citation
Yeon Hee Park et al. (2009). Interaction between BCL2 and Interleukin-10 Gene Polymorphisms
Alter Outcomes of Diffuse Large B-Cell Lymphoma following
Rituximab Plus CHOP Chemotherapy. Clinical Cancer Research, 15(6), 2107–2115. doi: 10.1158/1078-0432.CCR-08-1588
Type
Article
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-08-1588
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35479
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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