The Role of Cytokine Gene Polymorphisms in Colorectal Cancer and their interaction with Aspirin Use in the North East of Scotland

M. Macarthur, L. sharp, G. hold, J. little, Emad Munir El-Omar

Research output: Contribution to journalArticle

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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 (P-interaction = 0.03). Carriers of the variant IL-10-592 (A) allele, who produce less of the antiinflammatory 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 antiinflammatory 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.

Original languageEnglish
Pages (from-to)1613-1618
Number of pages5
JournalCancer Epidemiology, Biomarkers and Prevention
Volume14
Issue number7
DOIs
Publication statusPublished - 2005

Keywords

  • single nucleotide polymorphisms
  • interleukin-1 polymorphisms
  • gastric-cancer
  • increased risk
  • plasma-levels
  • IL-10 LOCUS
  • promoter
  • disease
  • frequency
  • haplotype

Cite this

The Role of Cytokine Gene Polymorphisms in Colorectal Cancer and their interaction with Aspirin Use in the North East of Scotland. / Macarthur, M.; sharp, L.; hold, G.; little, J.; El-Omar, Emad Munir.

In: Cancer Epidemiology, Biomarkers and Prevention, Vol. 14, No. 7, 2005, p. 1613-1618.

Research output: Contribution to journalArticle

Macarthur, M. ; sharp, L. ; hold, G. ; little, J. ; El-Omar, Emad Munir. / The Role of Cytokine Gene Polymorphisms in Colorectal Cancer and their interaction with Aspirin Use in the North East of Scotland. In: Cancer Epidemiology, Biomarkers and Prevention. 2005 ; Vol. 14, No. 7. pp. 1613-1618.
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N2 - 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 (P-interaction = 0.03). Carriers of the variant IL-10-592 (A) allele, who produce less of the antiinflammatory 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 antiinflammatory 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.

AB - 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 (P-interaction = 0.03). Carriers of the variant IL-10-592 (A) allele, who produce less of the antiinflammatory 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 antiinflammatory 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.

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KW - frequency

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