Artikel
Interaction between regular use of non-steroidal anti-inflammatory drugs, variants in inflammatory genes and risk of lymphoma
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Veröffentlicht: | 6. September 2007 |
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Background: Inflammation is an established risk factor for several cancer sites. Limited evidence suggests an importance of inflammatory processes also for the etiology of lymphomas. To further research in this area, we explored the role of genetic variants in key inflammatory factors, non-steroidal anti-inflammatory drug [NSAID] use, and their joined effects in lymphomagenesis.
Methods: In the context of a German population-based case-control study of 710 lymphoma cases and 710 age- and sex-matched controls, we examined the association of regular NSAID use and polymorphisms in prostaglandin-endoperoxide synthase 2 (COX2), prostaglandin E synthase (PTGES), interleukin-1-alpha (IL1A), IL1-beta (IL1B), and IL1 receptor antagonist (IL1RA) and the risk of lymphoma and main lymphoma subtypes (B-cell non-Hodgkin’s lymphoma [B-NHL], T-cell NHL [T-NHL], and Hodgkin’s lymphoma [HL]. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95%CI) between genotype or haplotype, regular NSAID use, and risk of lymphoma.
Results: None of the investigated polymorphisms was statistically significant associated with risk of lymphoma. Based on few cases, the COX2 rs2745557 A-allele and homozygosity of the IL1RN rs454078 T-allele conferred a 2.2-fold (95%CI=1.10-4.51) and 4.5-fold (95%CI=1.47-13.89) elevated risk for T-NHL. Regular NSAID use was associated with a slightly reduced risk of lymphoma (OR=0.79; 95%CI=0.57-1.09) and B-NHL (OR=0.77; 95%CI=0.55-1.08). We observed statistically significant interaction between ÍL1-haplotypes, regular NSAID use and B-NHL risk. IL-AACC- haplotype was associated with a statistically significant 44% increased risk for B-NHL among non-regular NSAID users (95%CI=1.03-2.04), but decreased risk for regular NSAID users (OR=0.25, 95%CI=0.07-0.93) (p-value for interaction = 0.006). A similar effect was seen for TACC-haplotype (p for interaction <0.001).
Conclusions: These results suggest a relevance of joint effects between NSAID use and IL1 haplotypes on the risk of B-NHL. Combined evaluations of inflammatory gene variants and environmental factors implicated in inflammatory processes will help to elucidate mechanisms underlying inter-individual differences in lymphoma risk.