METAANALYSIS OF STUDIES OF THE CYP2D6 POLYMORPHISM IN RELATION TO LUNG-CANCER AND PARKINSONS-DISEASE

Studies of associations between the CYP2D6 polymorphism and susceptibi lity to specific diseases, particularly lung cancer and Parkinsonism, have produced conflicting results with respect to an under or overrepr esentation of poor metabolizers. Accordingly, we have re-evaluated thi s primary research (18 studies on lung cancer and 18 on Parkinsonism) using meta-analysis. For lung cancer the median odds ratio (OR) was 0. 69 (95% confidence interval (CI) 0.52-0.90), which differed significan tly from unity (P < 0.007). A trial comprising 3000 patients and an eq ual number of control individuals would be required to demonstrate tha t this observation had arisen purely by chance (i.e. OR = 1), For Park inson's disease, the analysis gave an OR of 1.32 (95% CI 0.98-1,78), w hich was of borderline statistical significance (P < 0,074). If the on ly individual study that was statistically significant was excluded, t he P-value increased greatly to 0.489. A study of at least 500 patient s and an equal number of control individuals giving the same value as the current mean OR of 1.32 would be required to make the overall anal ysis statistically significant. In summary, poor metabolizers with res pect to CYP2D6 show a small decrease in susceptibility to lung cancer compared with extensive metabolizers and it is hard to justify further studies. The relationship between the CYP2D6 polymorphism and lung ca ncer, as a determinant of individual susceptibility, is not appreciabl e (OR = 0.69) compared with that between smoking and lung cancer (OR > 11). Nevertheless, the epidemiological impact on the number of poor m etabolizers who are protected from lung cancer may be considerable. Wi th regard to Parkinson's disease, additional well designed studies may allow a definitive conclusion, although any risk for poor metabolizer s is likely to be small and therefore of questionable clinical signifi cance. An important lesson from the current review of studies is that much time, effort, expense and patient inconvenience might have been a voided if more attention had been paid to appropriate study design, pa rticularly in the selection of control groups. Pharmacogenetics 8:227- 238 (C) 1998 Lippincott-Raven Publishers.