© 1992 Oxford University Press
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Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility
Imperial Cancer Research Fund, Molecular Pharmacology Group, Hugh Robson Building George Square, Edinburgh EH8 9XD
1Imperial Cancer Research Fund, Human Genetic Resources, Clare Hall Laboratories South Mimma, Potters Bar, Herts EN6 3LR
2Department of Radiotherapy, University of Edinburgh, Western General Hospital Edinburgh EH4 2XU
3Department of Pathology, University of Edinburgh, Medical School Teviot Place, Edinburgh EH8 9AG
4Leukaemia Research Fund Laboratories, Glasgow Royal Infirmaiy Castle St., Glasgow G4 OSF
5Department of Respiratoiy Medicine, University of Edinburgh, City Hospital Edinburgh EH 10 5SB
6Imperial Cancer Research Fund, Clinical Oncology, Churchill Hospital Headington, Oxford 0X3 7LJ, UK
2To whom correspondence should be addressed
There have been a series of reports on the association of a genetic polymorphism at the cytochrome P450 CYP2D6 gene locus with cancer susceptibility. Many of these reports have remained contradictory either because of small numbers of patients studied or because of the limitations and controversy surrounding the pharmacokinetic assay used to identify affected individuals (poor metabolizers; PMs). We have recently developed a DNA-based assay that will allow the unequivocal identification of poor metabolizers and have applied this to the study of 1635 patients with different forms of cancer. Out of 361 lung cancer patients studied no statistically significant change in the proportion of PMs relative to controls was found. However, a significant increase in the proportion of poor metabolizers or heterozygotes was seen in leukaemia, bladder cancer and melanoma patients. This could be explained by a role for CYP2D6 in carcinogen detoxification or by linkage to another cancer-causing gene.
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