title: The role of cytokine gene polymorphisms in colorectal cancer and their interaction with aspirin use in the northeast of Scotland.
abstract: The reduced risk of colorectal cancer associated with cyclooxygenase enzyme inhibitors, such as aspirin and other nonsteroidal anti-inflammatory drugs, strongly suggests that chronic inflammation is a key mediator in the development of colorectal cancer. This complements recent molecular evidence demonstrating an association between a number of proinflammatory genetic polymorphisms and risk of colorectal cancer. We assessed polymorphisms in the IL-1, IL-10, TNF-A, and TGF-B genes in a population-based case-control study of colorectal cancer cases (n = 264) and frequency-matched controls (n = 408) in the Northeast of Scotland and analyzed their interaction with regular aspirin use. There was no evidence of a relation between any of the individual polymorphisms, or pairs of polymorphisms, and risk of colorectal cancer. There was a significant interaction between the IL-10-592 C/A polymorphism and aspirin use (Pinteraction = 0.03). Carriers of the variant IL-10-592 (A) allele, who produce less of the anti-inflammatory cytokine interleukin-10, had a statistically significant 50% reduced risk of colorectal cancer when taking regular aspirin (odds ratio, 0.5; 95% confidence interval, 0.25-0.97), whereas risk was not reduced in carriers of the A allele who did not use aspirin, or among aspirin users with the CC genotype. It is possible that carriers of the mutant IL-10-592 allele are more likely to derive anti-inflammatory and chemopreventive benefits from aspirin in the presence of a lower production of their own endogenous anti-inflammatory interleukin-10. These results suggest that host genetics may play a role in predicting response to chemopreventive strategies. Confirmation of these findings in other populations is required.
authors: Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
authors: Mairi
authors: M
authors: Macarthur
authors: Linda
authors: L
authors: Sharp
authors: Georgina L
authors: GL
authors: Hold
authors: Julian
authors: J
authors: Little
authors: Emad M
authors: EM
authors: El-Omar
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012606:Scotland / Q000453:epidemiology; D012923:Social Class
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D001241:Aspirin