Rostami-Hodjegan A, Lennard M S, Woods H F, Tucker G T
University of Sheffield, Department of Medicine and Pharmacology, Royal Hallamshire Hospital, UK.
Pharmacogenetics. 1998 Jun;8(3):227-38. doi: 10.1097/00008571-199806000-00005.
Studies of associations between the CYP2D6 polymorphism and susceptibility to specific diseases, particularly lung cancer and Parkinsonism, have produced conflicting results with respect to an under or overrepresentation of poor metabolizers. Accordingly, we have re-evaluated this 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 significantly from unity (P < 0.007). A trail comprising 3000 patient and an equal number of control individuals would be required to demonstrate that this observation had arisen purely by chance (i.e. OR = 1). For Parkinson's disease, the analysis gave an OR of 1.32 (95% CI 0.98-1.78), which was of borderline statistical significance (P < 0.074). If the only individual study that was statistically significant was excluded, the P-value increased greatly to 0.489. A study of at least 500 patients 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 analysis statistically significant. In summary, poor metabolizers with respect to CYP2D6 show a small decrease in susceptibility to lung cancer compared with extensive metabolizers and its is hard to justify further studies. The relationship between the CYP2D6 polymorphism and lung cancer, as a determinant of individual susceptibility, is not appreciable (OR = 0.69) compared with that between smoking and lung cancer (OR > 11). Nevertheless, the epidemiological impact on the number of poor metabolizers who are protected from lung cancer may be considerable. With regard to Parkinson's disease, additional well designed studies may allow a definitive conclusion, although any risk for poor metabolizers is likely to be small and therefore of questionable clinical significance. An important lesson from the current review of studies is that much time, effort, expense and patient inconvenience might have been avoid if more attention had been paid to appropriate study design particularly in the selection of control groups.
关于CYP2D6基因多态性与特定疾病易感性之间的关联研究，尤其是肺癌和帕金森病，在代谢不良者的比例过高或过低方面产生了相互矛盾的结果。因此，我们使用荟萃分析重新评估了这项初步研究（18项关于肺癌的研究和18项关于帕金森病的研究）。对于肺癌，中位比值比（OR）为0.69（95%置信区间（CI）0.52 - 0.90），与1有显著差异（P < 0.007）。需要一项包含3000名患者和同等数量对照个体的试验，才能证明这一观察结果纯粹是偶然出现的（即OR = 1）。对于帕金森病，分析得出的OR为1.32（95% CI 0.98 - 1.78），具有边缘统计学意义（P < 0.074）。如果排除唯一一项具有统计学意义的个体研究，P值将大幅增加至0.489。需要至少一项对500名患者和同等数量对照个体进行的研究，且得出与当前平均OR值1.32相同的结果，才能使整体分析具有统计学意义。总之，与广泛代谢者相比，CYP2D6代谢不良者对肺癌的易感性略有降低，进一步研究的合理性不足。与吸烟和肺癌之间的关系（OR > 11）相比，CYP2D6基因多态性与肺癌作为个体易感性决定因素之间的关系并不明显（OR = 0.69）。然而，对受肺癌保护的代谢不良者数量的流行病学影响可能相当大。关于帕金森病，尽管代谢不良者的任何风险可能很小，因此临床意义存疑，但更多精心设计的研究可能会得出明确结论。当前研究综述的一个重要教训是，如果在研究设计尤其是对照组的选择上给予更多关注，许多时间、精力、费用和患者的不便可能是可以避免的。
