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.
- Polymorphisms in immune function genes and non-Hodgkin lymphoma survival
Journal of Cancer Survivorship
Volume 6, Issue 1 , pp 102-114
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- Springer US
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- Non-Hodgkin lymphoma
- Single nucleotide polymorphisms
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- Author Affiliations
- 1. School of Public Health, Yale University, New Haven, CT, USA
- 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA
- 5. Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, NIH/DHHS, 6120 Executive Blvd, EPS 8111, Bethesda, MD, 20892, USA
- 3. Department of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA
- 4. Cancer Institute/Hospital, Chinese Academy of Medical Siences, Beijing, China