Joint effect between regular use of non-steroidal anti-inflammatory drugs, variants in inflammatory genes and risk of lymphoma
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Limited evidence suggests the importance of inflammatory processes for the etiology of lymphomas. To further research in this area, we investigated the role of genetic variants in key inflammatory factors, non-steroidal anti-inflammatory drug [NSAID] use, and their joint effect in lymphomagenesis.
The study comprised 710 case–control pairs, matched for gender, age, and study region. We examined the association of regular NSAID use and polymorphisms in prostaglandin-endoperoxide synthase-2 (COX2), prostaglandin E synthase (PTGES), interleukin-1 alpha (IL1A), IL-1 beta (IL1B), and IL-1 receptor antagonist (IL1RA), and lymphoma risk by applying logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI).
Regular NSAID use was associated with a slightly reduced risk of B-NHL (OR = 0.8, 95% CI = 0.6–1.1). For T-NHL, the COX2 rs2745557 A-allele conferred a 2.2-fold (95% CI = 1.1–4.5) and homozygosis for the IL1RN rs454078 T-allele was associated with a 4.5-fold (95% CI = 1.4–13.9) elevated risk, however, based on sparse data. IL1 haplotype 5 was associated with a statistically significant 43% increased risk for B-NHL among non-regular users of NSAIDs, but a 70% decreased risk for regular users (p-value for interaction < 0.001).
These results suggest the relevance of joint effects between NSAID use and IL1 haplotypes on the risk of B-NHL.
KeywordsLymphoma Non-steroidal anti-inflammatory drugs (NSAIDs) Single nucleotide polymorphism (SNP)
We are indebted to the participants of the study and to the many colleagues who supported the performance of the study. A detailed list is presented in previous publications . For excellent technical assistance we thank Marlen Auer, Bettina Ehret, and Sandra Patommel and Stefan Wilkening for his support with TaqMan genotyping. Furthermore, we thank Jutta Kneisel and Sabine Behrens for their help with drug coding and statistical analysis, respectively. The study was funded by the Federal Office for Radiation Protection (StSch4261 and StSch4420) and supported by a Deutsche Forschungsgemeinschaft Grant BE 3906//2-1 (LB). The European Community supported the set up of a common protocol for assessment of occupational exposures (SOC 98 201307 05F02) and implementation of additional study areas (QLK4-CT-2000-00422). Genotyping was supported by the German José Carreras Leukaemia foundation (DJCLS_R04/08).
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