Joint effect between regular use of non-steroidal anti-inflammatory drugs, variants in inflammatory genes and risk of lymphoma.
OBJECTIVE
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
These results suggest the relevance of joint effects between NSAID use and IL1 haplotypes on the risk of B-NHL.
Molecular Tumour Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany.
Birgit
B
Hoeft
Nikolaus
N
Becker
Evelin
E
Deeg
Lars
L
Beckmann
Alexandra
A
Nieters
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000071876:Prostaglandin-E Synthases; D012306:Risk
D000894:Anti-Inflammatory Agents, Non-Steroidal; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases