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Carcinogenesis, Vol. 23, No. 4, 665, April 2002
© 2002 Oxford University Press

LETTER TO THE EDITOR

Association of CYP2C9 genotypes leading to high enzyme activity and colorectal cancer risk

Ümit Yasar,2, Erik Eliasson and Marja-Liisa Dahl1

Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden and
1 Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden

Dear Sir,

We read with interest the article by Martinez et al. (1) regarding a possible association between CYP2C9 genotypes leading to high enzyme activity and colorectal cancer. An important issue in this study is the selection of a control group consisting of healthy Spanish volunteers rather than patients in the same age group with benign diseases of the colon.

The same research group has reported recently the allele frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 as 0.695, 0.143 and 0.162, respectively, in 157 Spanish healthy volunteers as `high frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population (2)'. These figures are almost identical to those reported by Martinez et al. (1). The CYP2C9*3 variant is grossly over-represented in this Caucasian population. As a consequence of this, the frequency of CYP2C9*1 is lower than in several other Caucasian studies (3–5, and references therein), and not consistent with other reports as mentioned in the article. The frequencies of the CYP2C9 variant alleles in the colorectal cancer patients are very similar to those reported in healthy volunteers from other Caucasian populations (5).

In conclusion, the suggested association between the CYP2C9 genotype and colorectal cancer is based on an atypical allelic distribution in the control group of healthy volunteers, and should be interpreted with caution.

Notes

2 To whom correspondence should be addressed Email: umit.yasar{at}labtek.ki.se Back

References

  1. Martinez,C., Garcia-Martin,E., Ladero,J.M., Sastre,J., Garcia-Gamito,F., Diaz-Rubio,M. and Agundez,J.A. (2001) Association of CYP2C9 genotypes leading to high enzyme activity and colorectal cancer risk. Carcinogenesis, 22, 1323–1326.[Abstract/Free Full Text]
  2. Garcia-Martin,E., Martinez,C., Ladero,J.M., Gamito,F.J. and Agundez,J.A. (2001) High frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population. Eur. J. Clin. Pharmacol., 57, 47–49.[Web of Science][Medline]
  3. Miners,J.O. and Birkett,D.J. (1998) Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol., 45, 525–538.[Web of Science][Medline]
  4. Yasar,Ü., Eliasson,E., Dahl,M.L., Johansson,I., Ingelman-Sundberg,M. and Sjöqvist,F. (1999) Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population. [Erratum published in Biochem. Biophys. Res. Commun., 1999, 258, 227]. Biochem. Biophys. Res. Commun., 254, 628–631.[Web of Science][Medline]
  5. Scordo,M.G., Aklillu,E., Yasar,Ü., Dahl,M.-L., Spina,E. and Ingelman-Sundberg,M. (2001) Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a Black-African population. Br. J. Clin. Pharmacol., 52, 447–450.[Web of Science][Medline]
Received December 12, 2001; accepted January 13, 2002.


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