Sugawara T, Nomura E, Sagawa T, Sakuragi N, Fujimoto S
Departments of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Int J Gynecol Cancer. 2003 Nov-Dec;13(6):785-90. doi: 10.1111/j.1525-1438.2003.13607.x.
The incidence of endometrial cancer and ovarian cancer in Japan has been increasing in recent years. Results of epidemiologic studies suggest that the onset and multiplication of these cancers are associated with estrogen. Estrogens are metabolized by cytochrome P450 1A1 (CYP1A1) and converted into catecholestrogens, which are carcinogens. CYP1A1 has several polymorphisms, the major one being T6235C transition in the non-coding 3'-flanking region (MspI polymorphism), and another being A4889G transition in exon 7 (Ile/Val polymorphism). These polymorphisms can affect the metabolites of estrogens and contribute to the susceptibility to gynecological malignancy. In this study, to determine whether CYP1A1 polymorphism plays a role in the development of gynecological malignancy in the Japanese population, we assessed the association of CYP1A1 polymorphism in Japanese patients with gynecological malignancy in comparison to that in controls. The odds ratios (ORs) of Ile/Val polymorphism were 1.16 in ovarian cancer patients and 1.70 in endometrial cancer patients. The ORs of MspI polymorphism were 1.33 in ovarian cancer patients and 0.88 in endometrial cancer patients. No significant association was found between these CYP1A1 polymorphisms and gynecological malignancy. Although the frequency of CYP1A1 polymorphism in the Japanese population is higher than that in the Caucasian population, CYP1A1 polymorphism is not related to gynecological malignancies in Japanese population.
近年来,日本子宫内膜癌和卵巢癌的发病率一直在上升。流行病学研究结果表明,这些癌症的发生和增殖与雌激素有关。雌激素通过细胞色素P450 1A1(CYP1A1)代谢并转化为儿茶酚雌激素,而儿茶酚雌激素是致癌物。CYP1A1有几种多态性,主要的一种是在非编码3'侧翼区域的T6235C转换(MspI多态性),另一种是外显子7中的A4889G转换(Ile/Val多态性)。这些多态性会影响雌激素的代谢产物,并导致对妇科恶性肿瘤的易感性。在本研究中,为了确定CYP1A1多态性是否在日本人群妇科恶性肿瘤的发生中起作用,我们评估了日本妇科恶性肿瘤患者中CYP1A1多态性与对照组的相关性。Ile/Val多态性在卵巢癌患者中的比值比(OR)为1.16,在子宫内膜癌患者中为1.70。MspI多态性在卵巢癌患者中的OR为1.33,在子宫内膜癌患者中为0.88。未发现这些CYP1A1多态性与妇科恶性肿瘤之间存在显著关联。尽管日本人群中CYP1A1多态性的频率高于白种人群,但CYP1A1多态性与日本人群的妇科恶性肿瘤无关。