No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk.
OBJECTIVE
To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with risk of colon cancer.


METHODS
NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly, enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms (SNPs) in the COX2 and UGT1A6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.


RESULTS
No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk (P > 0.05), and we did not observe that these variants modify the protective effect of NSAIDs (P > 0.05). We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.


CONCLUSIONS
Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.
Thompson
Cheryl-L
CL
Department of Family Medicine, Research Division, Case Western Reserve University, 11001 Cedar Ave., Suite 306, Cleveland, Ohio 44106-7136, United States.
Plummer
Sarah-J
SJ
Merkulova
Alona
A
Cheng
Iona
I
Tucker
Thomas-C
TC
Casey
Graham
G
Li
Li
L
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase