Goodman Marc T, Lurie Galina, Thompson Pamela J, McDuffie Katharine E, Carney Michael E
Cancer Epidemiology Program, Cancer Research Center of Hawaii, Honolulu, Hawaii, USA.
Endocr Relat Cancer. 2008 Dec;15(4):1055-60. doi: 10.1677/ERC-08-0104. Epub 2008 Jul 30.
Although the role of estrogen in the etiology of ovarian cancer is uncertain, there is increasing evidence that hormone replacement therapy is a risk factor for ovarian malignancy. The production of estrogen involves the conversion of androgens via P450 aromatase, encoded by the CYP19A1 gene. Genetic variation in two CYP19A1 single-nucleotide polymorphisms (SNPs), rs749292 and rs727479, has been found to produce 10-20% increases in estrogen levels among postmenopausal women. We tested the hypothesis that these SNPs were associated with the risk of ovarian cancer in a population-based case-control study in Hawaii, including 367 histologically confirmed epithelial ovarian cancer cases and 602 age- and ethnicity-matched controls. The A allele of rs749292 was positively associated with ovarian cancer risk in a codominant model for all races combined (AG versus AA genotype: odds ratio (OR), 1.48 and 95% confidence interval (CI, 1.07-2.04); GG versus AA: OR, 1.87 (CI, 1.24-2.82); P(trend)=0.002). Similar significant associations of the rs749292 A allele on the risk of ovarian cancer were found among Caucasian and Japanese women. No relation of the rs727479 SNP to ovarian cancer risk was observed overall, although Caucasian women carrying the variant A allele compared with women with an CC genotype had an OR of 2.91 (CI, 1.15-7.37). These data suggest CYP19A1 variants may influence susceptibility to ovarian cancer.
尽管雌激素在卵巢癌病因学中的作用尚不确定，但越来越多的证据表明激素替代疗法是卵巢恶性肿瘤的一个危险因素。雌激素的产生涉及雄激素通过由CYP19A1基因编码的P450芳香化酶的转化。已发现CYP19A1两个单核苷酸多态性（SNP），即rs749292和rs727479的基因变异，会使绝经后女性的雌激素水平升高10%至20%。在夏威夷一项基于人群的病例对照研究中，我们检验了这些SNP与卵巢癌风险相关的假设，该研究包括367例经组织学确诊的上皮性卵巢癌病例和602例年龄及种族匹配的对照。在所有种族合并的共显性模型中，rs749292的A等位基因与卵巢癌风险呈正相关（AG与AA基因型：优势比（OR）为1.48，95%置信区间（CI）为1.07 - 2.04；GG与AA：OR为1.87（CI为1.24 - 2.82）；P（趋势）=0.002）。在白种人和日本女性中也发现了rs749292的A等位基因与卵巢癌风险有类似的显著关联。尽管携带变异A等位基因的白种女性与CC基因型女性相比，OR为2.91（CI为1.15 - 7.37），但总体上未观察到rs727479 SNP与卵巢癌风险的关系。这些数据表明CYP19A1变异可能影响卵巢癌的易感性。
