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Journal of Clinical Oncology, Vol 26, No 10 (April 1), 2008: pp. 1766-1767 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.5929
Ethnic Considerations in Pharmacogenetic StudiesSt Joseph's Hospice; Interstitial Lung Disease Unit, Department of Population Genetics and Gene Therapy, National Heart and Lung Institute, Imperial College, London, United Kingdom
Interstitial Lung Disease Unit, Department of Population Genetics and Gene Therapy, National Heart and Lung Institute, Imperial College, London, United Kingdom
St Joseph's Hospice; Interstitial Lung Disease Unit, Department of Population Genetics and Gene Therapy, National Heart and Lung Institute, Imperial College, London, United Kingdom To the Editor: Establishing correlations between genotype and outcome is a difficult task in complex diseases because of variable interindividual genetic makeup and interactions with specific environmental exposures. Marsh et al1 examined polymorphisms in 16 key genes from influential taxane and platinum pathways. They did not detect any significant reproducible associations with either clinical outcome or toxicity in a large cohort of patients enrolled onto the Scottish Randomised Trial in Ovarian Cancer.2 Of note, previously reported genetic associations with response to paclitaxel in ovarian cancer, such as ABCB1 2677G > T/A (Swedish study3) were not replicated in this cohort. Obviously, there is a need for large worldwide population samples and reliable replication of results to help identify the impact of genetic variants on diagnosis, prognosis, or treatment. However, to identify a potential association of small magnitude which may be part of a network of aggravating and protecting genes, a population with exacting phenotypic characterization and ethnic/genetic homogeneity is essential. The Scottish Randomised Trial in Ovarian Cancer is an international multicenter study and as such contains patients from many different ethnic backgrounds. Replicating single-population results in ethnically mixed populations is difficult. Small but significant differences in allele frequencies in individual ethnic groups may lead to both false-positive and false-negative results. The volume of data presented in this study is invaluable to progress in this field. However, an ethnic stratification of the data would facilitate additional assessment of polymorphic relevance in specific ethnic populations and potentially impact the development of personalized disease management in the future. We look forward to seeing more results presented from this cohort. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Marsh S, Paul J, King C, et al: pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: The Scottish randomised trial in ovarian cancer. J Clin Oncol 25:4528-4535, 2007 2. Vasey PA, Jayson GC, Gordon A, et al: Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96:1682-1691, 2004 3. Gréen H, Söderkvist P, Rosenberg P, et al: Mdr-1 single neucleotide polymorphism in ovarian cancer tissue: G2677T/A correlates to response to paclitaxel chemotherapy. Clin Cancer Res 12:854-859, 2006 Related Reply
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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