Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma.
OBJECTIVE
Cyclooxygenase (COX) enzymes, COX1 and COX2, are key in converting arachidonic acid (AA) into prostaglandins that have been associated with colorectal carcinogenesis. The aim of our study was to investigate associations of polymorphisms in COX genes, alone and in interaction with exposures known to be related to inflammation and AA metabolism, with risk of colorectal adenomas.


METHODS
In a community-, colonoscopy-based case-control study with 162 incident, sporadic colorectal adenoma cases and 211 controls, we investigated associations of two promoter polymorphisms (-842 A > G in COX1 and -765 G > C in COX2) and two polymorphisms in the 3'-UTR of COX2 (8473 T > C and 9850 A > G) with risk of adenomas. Multiple logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma after adjusting for potential confounders.


RESULTS
Overall, there was no evidence for an association between any of the four polymorphisms and colorectal adenomas. However, we found a statistically significant interaction between the COX2 8473 T > C polymorphism and nonsteroidal anti-inflammatory drug (NSAIDs) use (P (interaction) = 0.03): The greatest reduced risk was observed for individuals with the 8473 C variant allele who also regularly used NSAIDs (OR = 0.35, 95% CI 0.16-0.75).


CONCLUSIONS
These results suggest that the C allele of COX2 8473 T > C polymorphism may interact with NSAIDs to reduce risk for colorectal adenoma.
Gong
Zhihong
Z
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Bostick
Roberd M
RM
Xie
Dawen
D
Hurley
Thomas G
TG
Deng
Zonglin
Z
Dixon
Dan A
DA
Zhang
Jinhui
J
Hebert
James R
JR
D000236:Adenoma / Q000201:enzymology* / Q000235:genetics; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human