Protective effect of NSAIDs on cancer and influence of COX-2 C(-765G) genotype.
OBJECTIVE
Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common non-skin related cancers and modification by COX-2 G(-765)C genotype.


METHODS
7621 participants of The Rotterdam Study were included. In a mean follow up period of 10 years, 720 colorectal, lung, breast or prostate cancers occurred. Cumulative NSAID use was calculated per NSAID class. Individual associations of NSAID use and COX-2 G(-765)C genotype on cancer risk were explored with Cox' proportional hazard models. Next, the association of NSAIDs and cancer stratified by COX-2 genotype was studied. Finally, the effect of combinations of NSAID use and COX-2 genotype on survival times was investigated.


RESULTS
All NSAID classes were associated with a reduced risk of colorectal cancer but not of other cancers. No associations between COX-2 genotype and incident cancer, overall or cancer specific mortality were observed. COX-selective NSAIDs showed modest further risk reduction. Survival times were more than twice as long for carriers of a COX-2 C(-765) allele with colorectal cancer who used NSAIDs in the five years prior to diagnosis than for patients homozygous for the wild type (G(-765)) without NSAID use (p = 0.007).


CONCLUSIONS
Our results confirm the protective effect of NSAID use on colorectal cancer. Individuals diagnosed with colorectal cancer who carry a COX-2 C(-765) allele and are on NSAIDs have an increased survival in comparison to non-users with the wild type (G(-765)).
Siemes
C
C
Department of Epidemiology & Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands. b.stricker@erasmusmc.nl
Visser
L E
LE
Coebergh
J W W
JW
Hofman
A
A
Uitterlinden
A G
AG
Stricker
B H Ch
BH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001483:Base Sequence; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D051546:Cyclooxygenase 2