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NSAID use modified link between COX2, colorectal cancer risk
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AACR 100th Annual Meeting
Although COX1 and COX2 polymorphisms may not predict risk for colorectal cancer, researchers have demonstrated that the use of nonsteroidal anti-inflammatory drugs may alter the association between COX2 and colorectal cancer risk.
“One main result was that one genetic variant in COX2 was associated with a decreased risk of colorectal cancer,” Anna E. Coghill, MPH, graduate research assistant, Fred Hutchinson Cancer Research Center, presented the data at the AACR 100th Annual Meeting.
Coghill and colleagues used data from the Colon Cancer Family Registry to identify 2,511 sibling pairs to examine the role of 17 COX1 and 13 COX2 single nucleotide polymorphisms in colorectal cancer risk, both alone and in combination with aspirin and an NSAID.
The researchers found little evidence of an association between COX1 and COX2 variations and a modified risk for colorectal cancer. However, they did observe an interaction between regular NSAID use and SNPs rs12042763 (P=.03) and rs2745557 (P=.02) — both in the COX2 enzyme — though the researchers are unaware of their functional significance.
The presence of COX2 SNP rs4648261 was associated with a 40% (range 10% to 60%) decrease in colorectal cancer risk; no other SNP was associated with reduced risk. However, the researchers did observe an increase in colorectal cancer risk among patients with rs12042763 and rs2745557 variants who did not use NSAIDs. According to Coghill, this finding suggests that some patients may benefit from NSAIDs more than others.
“This research doesn’t have direct clinical implication right now, but we are examining these variants in other populations and we’re looking at more variants,” Coghill said. “COX2 and COX1 are important in this pathway and it’s something that we need to study further.”
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