Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

Cerhan, James R.; Wang, Sophia; Maurer, Mathew S.; Ansell, Stephen M.; Geyer, Susan; Cozen, Wendy; Morton, Lindsay M.; Davis, Scott; Severson, Richard K.; Rothman, Nathaniel; Lynch, Charles F.; Wacholder, Sholom; Chanock, Stephen J.; Habermann, Thomas M.; Hartge, Patricia

doi:10.1182/blood-2006-11-058040

Cited by 108 publications

(105 citation statements)

References 50 publications

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“…Similar work has identified a potential role for SNPs in the genes encoding IL8, IL2, IL12B, and IL1RN in patients with follicular lymphoma (FL). 15 Other work has identified polymorphisms in several immunoregulatory genes 16 and HLA 17 as potential contributing factors in patients with lymphoma.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

Host Factors for Risk and Survival in Lymphoma

Davé

2010

Hematology

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All cancers arise from complex interactions between aspects of the patient (host) biology and the environment. Once tumors arise, they frequently remain dependent on interactions with their microenvironment for their growth and proliferation. In this review, we examine the contributions of the host genetics and environmental exposures to the development of lymphoma. We will further examine the interactions of the tumor and the microenvironment that influence tumor growth and proliferation.Most tumor cells cannot survive for long when taken outside their immediate environment. This indicates a level of dependence on secreted factors or direct cellular interactions with the microenvironment that provides survival signals. This dependence may arise from normal interactions of the normal cell counterpart or it might arise from new, abnormal interactions that arise from the tumor biology. The precancer host biology itself may have a role in either promoting tumor growth or permissive growth by either harboring polymorphisms that, in the right context, promote tumor growth, or through behaviors that increase exposure to elements that promote carcinogenesis.Emerging technologies have provided new insights into the biology of a number of lymphomas. These technologies include microarrays that have enabled gene expression profiling to define the role of malignant and nonmalignant cells in the biology of lymphomas.Herein, we review the known contribution of the tumor microenvironment and host biology to the risk of developing lymphoma and the role of inherited and acquired host factors in disease progression and prognosis in patients with lymphoma. We will examine the tumor "macro" environment (ie, the biology of the patient [host]) and the tumor "micro" environment that contribute to the observed malignant phenotype.

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Section: Genetic Risk Factorsmentioning

confidence: 99%

Host Factors for Risk and Survival in Lymphoma

Davé

2010

Hematology

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“…The IL-10/ bcl-2-mediated pathway may not explain the entire mechanism of action of R-CHOP toward DLBCL. Cerhan et al (34) showed that the multiple candidate gene polymorphism approach could stratify patients with follicular lymphoma according to their prognosis; therefore, further study will help direct the multiple candidate gene polymorphism approach in targeting multiple potential drug resistance pathways in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

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

Park

Sohn

Kim

et al. 2009

Clinical Cancer Research

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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), +21A>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 1to 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.

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“…88,89 Other strategies have explored gene expression profiles to develop molecular predictors of response to treatment, 90 revealing microenvironment signatures associated with survival. 91,92 potentially transferable to clinical practice. [93][94][95][96] The use of such signatures as a prognostic tool for the stratification of patients with low tumor burden also remains to be explored.…”

Section: Clinical Perspectivesmentioning

confidence: 99%