Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Sep 24;79(1):168–171. doi: 10.1038/sj.bjc.6690028

Microsomal epoxide hydrolase gene polymorphism and susceptibility to colon cancer

D J Harrison 1, A L Hubbard 1, J MacMillan 1, A H Wyllie 1, C A D Smith 1
PMCID: PMC2362155  PMID: 10408710

Abstract

We examined polymorphisms in exons 3 and 4 of microsomal epoxide hydrolase in 101 patients with colon cancer and compared the results with 203 control samples. The frequency of the exon 3 T to C mutation was higher in cancer patients than in controls (odds ratio 3.8; 95% confidence intervals 1.8–8.0). This sequence alteration changes tyrosine residue 113 to histidine and is associated with lower enzyme activity when expressed in vitro. This suggests that putative slow epoxide hydrolase activity may be a risk factor for colon cancer. This appears to be true for both right- and left-sided tumours, but was more apparent for tumours arising distally (odds ratio 4.1; 95% confidence limits 1.9–9.2). By contrast, there was no difference in prevalence of exon 4 A to G transition mutation in cancer vs controls. This mutation changes histidine residue 139 to arginine and produces increased enzyme activity. There was no association between epoxide hydrolase genotype and abnormalities of p53 or Ki- Ras. © 1999 Cancer Research Campaign

Keywords: epoxide hydrolase, colon cancer, polymorphism, cancer risk

Full Text

The Full Text of this article is available as a PDF (42.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brockmöller J., Cascorbi I., Kerb R., Roots I. Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Cancer Res. 1996 Sep 1;56(17):3915–3925. [PubMed] [Google Scholar]
  2. Cantlay A. M., Lamb D., Gillooly M., Norrman J., Morrison D., Smith C. A., Harrison D. J. Association between the CYP1A1 gene polymorphism and susceptibility to emphysema and lung cancer. Clin Mol Pathol. 1995 Aug;48(4):M210–M214. doi: 10.1136/mp.48.4.m210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantlay A. M., Smith C. A., Wallace W. A., Yap P. L., Lamb D., Harrison D. J. Heterogeneous expression and polymorphic genotype of glutathione S-transferases in human lung. Thorax. 1994 Oct;49(10):1010–1014. doi: 10.1136/thx.49.10.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chenevix-Trench G., Young J., Coggan M., Board P. Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis. 1995 Jul;16(7):1655–1657. doi: 10.1093/carcin/16.7.1655. [DOI] [PubMed] [Google Scholar]
  5. Craft J. A., Bulleid N. J., Jackson M. R., Burchell B. Induction of microsomal epoxide hydrolase by nitrosamines in rat liver. Effect on messenger ribonucleic acids. Biochem Pharmacol. 1988 Jan 15;37(2):297–302. doi: 10.1016/0006-2952(88)90732-0. [DOI] [PubMed] [Google Scholar]
  6. Cripps K. J., Purdie C. A., Carder P. J., White S., Komine K., Bird C. C., Wyllie A. H. A study of stabilisation of p53 protein versus point mutation in colorectal carcinoma. Oncogene. 1994 Sep;9(9):2739–2743. [PubMed] [Google Scholar]
  7. Giovannucci E., Willett W. C. Dietary factors and risk of colon cancer. Ann Med. 1994 Dec;26(6):443–452. doi: 10.3109/07853899409148367. [DOI] [PubMed] [Google Scholar]
  8. Hassett C., Aicher L., Sidhu J. S., Omiecinski C. J. Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Mol Genet. 1994 Mar;3(3):421–428. doi: 10.1093/hmg/3.3.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hassett C., Lin J., Carty C. L., Laurenzana E. M., Omiecinski C. J. Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic expression. Arch Biochem Biophys. 1997 Jan 15;337(2):275–283. doi: 10.1006/abbi.1996.9794. [DOI] [PubMed] [Google Scholar]
  10. Hubbard A. L., Harrison D. J., Moyes C., Wyllie A. H., Cunningham C., Mannion E., Smith C. A. N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions. Gut. 1997 Aug;41(2):229–234. doi: 10.1136/gut.41.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ilett K. F., Ingram D. M., Carpenter D. S., Teitel C. H., Lang N. P., Kadlubar F. F., Minchin R. F. Expression of monomorphic and polymorphic N-acetyltransferases in human colon. Biochem Pharmacol. 1994 Mar 2;47(5):914–917. doi: 10.1016/0006-2952(94)90493-6. [DOI] [PubMed] [Google Scholar]
  12. Lancaster J. M., Brownlee H. A., Bell D. A., Futreal P. A., Marks J. R., Berchuck A., Wiseman R. W., Taylor J. A. Microsomal epoxide hydrolase polymorphism as a risk factor for ovarian cancer. Mol Carcinog. 1996 Nov;17(3):160–162. doi: 10.1002/(SICI)1098-2744(199611)17:3<160::AID-MC8>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  13. Lang N. P., Chu D. Z., Hunter C. F., Kendall D. C., Flammang T. J., Kadlubar F. F. Role of aromatic amine acetyltransferase in human colorectal cancer. Arch Surg. 1986 Nov;121(11):1259–1261. doi: 10.1001/archsurg.121.11.1259. [DOI] [PubMed] [Google Scholar]
  14. Omiecinski C. J., Aicher L., Holubkov R., Checkoway H. Human peripheral lymphocytes as indicators of microsomal epoxide hydrolase activity in liver and lung. Pharmacogenetics. 1993 Jun;3(3):150–158. doi: 10.1097/00008571-199306000-00005. [DOI] [PubMed] [Google Scholar]
  15. Probst-Hensch N. M., Haile R. W., Ingles S. A., Longnecker M. P., Han C. Y., Lin B. K., Lee D. B., Sakamoto G. T., Frankl H. D., Lee E. R. Acetylation polymorphism and prevalence of colorectal adenomas. Cancer Res. 1995 May 15;55(10):2017–2020. [PubMed] [Google Scholar]
  16. Smith C. A., Harrison D. J. Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet. 1997 Aug 30;350(9078):630–633. doi: 10.1016/S0140-6736(96)08061-0. [DOI] [PubMed] [Google Scholar]
  17. Strange R. C., Matharoo B., Faulder G. C., Jones P., Cotton W., Elder J. B., Deakin M. The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma. Carcinogenesis. 1991 Jan;12(1):25–28. doi: 10.1093/carcin/12.1.25. [DOI] [PubMed] [Google Scholar]
  18. Tomlinson I., Ilyas M., Novelli M. Molecular genetics of colon cancer. Cancer Metastasis Rev. 1997 Jun;16(1-2):67–79. doi: 10.1023/a:1005744323215. [DOI] [PubMed] [Google Scholar]
  19. Wohlleb J. C., Hunter C. F., Blass B., Kadlubar F. F., Chu D. Z., Lang N. P. Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations. Int J Cancer. 1990 Jul 15;46(1):22–30. doi: 10.1002/ijc.2910460107. [DOI] [PubMed] [Google Scholar]
  20. Yang E. K., Radominska A., Winder B. S., Dannenberg A. J. Dietary lipids coinduce xenobiotic metabolizing enzymes in rat liver. Biochim Biophys Acta. 1993 May 20;1168(1):52–58. doi: 10.1016/0005-2760(93)90265-b. [DOI] [PubMed] [Google Scholar]
  21. Yang S. K. Stereoselectivity of cytochrome P-450 isozymes and epoxide hydrolase in the metabolism of polycyclic aromatic hydrocarbons. Biochem Pharmacol. 1988 Jan 1;37(1):61–70. doi: 10.1016/0006-2952(88)90755-1. [DOI] [PubMed] [Google Scholar]
  22. Zhong S., Wyllie A. H., Barnes D., Wolf C. R., Spurr N. K. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis. 1993 Sep;14(9):1821–1824. doi: 10.1093/carcin/14.9.1821. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES