Genetic polymorphisms affecting clinical outcomes in epithelial ovarian cancer patients treated with taxanes and platinum compounds: A Korean population-based study
Introduction
The primary standard treatment of epithelial ovarian cancer (EOC) consists of a maximal cytoreductive surgery and adjuvant taxane- and platinum-based chemotherapy [1]. However, clinical outcomes by taxane- and platinum-based chemotherapy are different in patients with EOC. Recent studies suggested that there are significant differences in drug resistance, toxicity and survival for individuals with different genetic polymorphisms in the patients because they can change the function of enzymes related with metabolisms of taxanes and platinum compounds [2], [3].
For example, ATP-binding cassette transporter B1 (ABCB1, Multidrug resistance 1) polymorphism may change the function of P-glycoprotein, by which taxanes can be extruded through the cell membranes [4], [5]. Besides, drug resistance to platinum compounds may be shown by increased tolerance to DNA damage by Excision repair cross-complementation group 1 (ERCC1) [6], [7], Excision repair cross-complementation group 2 (ERCC2, Xeroderma pigmentosum group D) [8], [9], and X-ray repair cross-complementing group 1 (XRCC1) polymorphisms [10], [11], and by increased detoxification thorough the conjugation with glutathione by glutathione-S-transferase (GST) polymorphism [12], [13].
Thus, the current study was designed to determine the affect of genetic polymorphisms on drug response, toxicity and survival in patients with EOC who received taxane- and platinum-based chemotherapy after surgery.
Section snippets
Study population
Clinical data were retrieved from a database of patients diagnosed with EOC between March 2001 and November 2006. Approval by the Institutional Review Board of Seoul National University Hospital was obtained in advance for the current study. The eligibility criteria were as follows: patients with a histological confirmation of EOC; those treated with maximal cytoreductive surgery followed by adjuvant taxane- and platinum-based chemotherapy; those with Eastern Cooperative Oncology Group
Patients' characteristics
A total of 118 patients with a median age of 50 years (range, 24–74 years) were enrolled in the current study. Among all patients, 60 (50.8%) were in menopause, According to the FIGO criteria, 28 (23.7%) patients were in stage I, 9 (7.6%) in stage II, 74 (62.8%) in stage III and 7 (5.9%) in stage IV. Tumor grade was G1 in 33 (28%), G2 in 21 (17.8%) and G3 in 64 (54.2%) of all patients. Histologically, 75 (63.6%) tumors were diagnosed as serous carcinoma, 22 (18.6%) as endometrioid carcinoma, 15
Discussion
Previous studies have shown that many different genes were associated with the metabolism of taxane (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, TP53, etc) and platinum compound (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, XRCC1, etc) [16]. However, we selected the 10 genetic polymorphisms associated with taxane- and platinum-based chemotherapy because the role of them has been focused on EOC in many studies [16], [17], [18], and the distribution of mutated alleles in
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
The authors wish to thank the Medical Research Collaborating Center (MRCC) in Seoul National University Hospital for statistical analysis. This study was supported by a grant (CRI-06-3) from the Cancer Research Institute, Seoul National University Research Fund. Moreover, we deeply appreciate the committee of the 39th Annual Meeting of the Society of Gynecologic Oncologists for giving us the opportunity to present in a Focused Plenary Session IV—Translational Research (Abstr. 34).
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