Polymorphisms in immune function genes and non-Hodgkin lymphoma survival
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Cytokines play a critical role in regulating the immune system. In the tumor microenvironment, they influence survival, proliferation, differentiation, and movement of both tumor and stromal cells, and regulate tumor interactions with the extracellular matrix. Given these biologic properties, there is reason to hypothesize that cytokine activity influences the pathogenesis of non-Hodgkin lymphoma (NHL).
We investigated the effect of genetic variation in cytokine genes on NHL prognosis and survival by evaluating genetic variation in individual SNPs as well as the combined effect of multiple deleterious genotypes. Survival information from 496 female incident NHL cases diagnosed during 1996–2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008. Survival analyses were conducted by comparing Kaplan-Meier curves and hazard ratios (HR) were computed using Cox proportional hazard models adjusting for demographic and tumor characteristics for genes that were suggested by previous studies to be associated with NHL survival.
We found that the variant IL6 genotype is significantly associated (HR = 0.42; 95%CI: 0.23–0.77) with a decreased risk of death, as well as relapse and secondary cancer occurrence, among those with NHL. We also found that risk of death, relapse, and secondary cancers varied by specific SNPs for the follicular, DLBCL, and CLL/SLL histologic types. We identified combinations of polymorphisms whose combined deleterious effect significantly alter overall NHL survival and disease-free survival.
Our study provides evidence that the identification of genetic polymorphisms in cytokine genes may help improve the prediction of NHL survival and prognosis.
KeywordsNon-Hodgkin lymphoma Cytokines Single nucleotide polymorphisms Survival
This research was supported in part by the Intramural Research Program of the NIH/National Cancer Institute [NCI], grant CA62006 from the NCI, by Hull Argall & Anna Grant 22067A from the Yale Cancer Center, and by Fogarty training grants 1D43TW008323-01 and 1D43TW007864-01 from the National Institute of Health [NIH]. This publication was made possible by CTSA Grant number UL1 RR024139 from the National Center for Research Resources [NCRR], a component of the NIH and NHL roadmap for medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR. This research was approved by the DPH HIC. Certain data used in this study were obtained from the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data.
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