Institute of Pharmacogenetics, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Oncol Res. 2010;18(7):343-7. doi: 10.3727/096504010x12626118079903.
The role of estrogens in ovarian carcinogenesis and progression of ovarian cancer is unclear. Cytochrome P450 is involved in estrogen metabolism, and polymorphisms have been associated with functional changes and risk for ovarian cancer. In this study, we investigated the impact of the CYP1A1 Ile462Val polymorphism upon tumor risk and disease progression in ovarian cancer patients. One hundred and eleven ovarian cancer patients who had been treated at the University Hospital of Essen between 1999 and 2007 and 119 age-matched healthy female controls were enrolled in this study. Genotyping was performed using PCR-RFLP. The distribution of genotypes was statistically significant different between ovarian cancer patients and healthy controls. We observed a significant association of the Ile allele with ovarian cancer (OR 2.6, 95% CI 1.5-4.7, p = 0.001). Clinical parameters such as overall survival, FIGO stage, grading, and age at diagnosis did not differ significantly. We observed a statistically significant association between the 462Val allele and platinum resistance, which was defined as a time interval < 6 months to disease progression after administration of a platinum-based primary chemotherapy (OR 5.9, 95% CI 1.5-23.2, p = 0.005). We observed a significant association between the presence of the 462Ile allele with ovarian cancer. While there is uncertainty about the potential involvement of CYP1A1 in the metabolism of platinum-containing agents, our findings suggest an association between the 462Val allele and the development of platinum resistance in ovarian tumors. If confirmed in a larger, independent collective, our findings would have important relevance with respect to the clinical consequences for the primary chemotherapy of ovarian cancer patients.
雌激素在卵巢癌发生和进展中的作用尚不清楚。细胞色素 P450 参与雌激素代谢，其多态性与功能变化和卵巢癌风险相关。在这项研究中，我们研究了 CYP1A1 Ile462Val 多态性对卵巢癌患者肿瘤风险和疾病进展的影响。本研究纳入了 111 名 1999 年至 2007 年在埃森大学医院接受治疗的卵巢癌患者和 119 名年龄匹配的健康女性对照者。采用 PCR-RFLP 法进行基因分型。基因型分布在卵巢癌患者和健康对照组之间存在统计学显著差异。我们观察到 Ile 等位基因与卵巢癌显著相关（OR 2.6，95%CI 1.5-4.7，p=0.001）。总生存、FIGO 分期、分级和诊断时年龄等临床参数无显著差异。我们观察到 462Val 等位基因与铂类耐药之间存在统计学显著关联，铂类耐药定义为在接受基于铂的一线化疗后疾病进展的时间间隔<6 个月（OR 5.9，95%CI 1.5-23.2，p=0.005）。我们观察到 462Ile 等位基因与卵巢癌的存在存在显著相关性。虽然 CYP1A1 参与含铂药物代谢的潜在作用尚不确定，但我们的研究结果提示 462Val 等位基因与卵巢肿瘤中铂类耐药的发生有关。如果在更大的独立队列中得到证实，我们的研究结果将对卵巢癌患者一线化疗的临床后果具有重要意义。
