Hosono Satoyo, Matsuo Keitaro, Ito Hidemi, Watanabe Miki, Hirose Kaoru, Nakanishi Toru, Tajima Kazuo, Tanaka Hideo
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Asian Pac J Cancer Prev. 2011;12(10):2747-52.
Extra-ovarian sex hormone production plays an important role in endometrial cancer in postmenopausal women. Aromatase, which is encoded by CYP19A1, is a key enzyme in estrogen biosynthesis after menopause. To examine the association between polymorphisms in CYP19A1 and endometrial cancer risk among postmenopausal Japanese women, we conducted a hospital-based case control study in 48 patients with histologically diagnosed incident endometrial cancer and 253 non-cancer control subjects. Information on lifestyle factors was obtained from a self-administered questionnaire. Twenty-five tag SNPs (single nucleotide polymorphisms) of CYP19A1 were examined by TaqMan methods and haplotype blocks were identified by LD analysis. Associations were assessed by an unconditional logistic regression model adjusted for potential confounders. We found no significant association between CYP19A1 genotypes and haplotypes and endometrial cancer risk. However, among women with a BMI (body mass index) >23, significantly positive associations were observed for rs2899473, rs1865803, rs16964220, rs2008691, rs17647707, rs17647719, rs1902586, rs936306, and rs1004982, while negative associations were seen for rs1902585, rs752760 and rs2445768. These showed significant interactions with BMI. Further, of the six haplotype blocks identified, the haplotype CTT of block 1, GATA of block 5 and CA of block 6 showed statistically significant interactions with BMI. These results suggest that CYP19A1 polymorphisms might play an important role in the etiology of endometrial cancer, and that the effect of these polymorphisms might be influenced by BMI.
卵巢外性激素的产生在绝经后女性子宫内膜癌中起重要作用。由CYP19A1编码的芳香化酶是绝经后雌激素生物合成中的关键酶。为了研究CYP19A1基因多态性与日本绝经后女性子宫内膜癌风险之间的关联，我们在48例经组织学诊断为新发子宫内膜癌的患者和253例非癌症对照受试者中进行了一项基于医院的病例对照研究。生活方式因素的信息通过自填问卷获得。通过TaqMan方法检测了CYP19A1的25个标签单核苷酸多态性（SNP），并通过连锁不平衡分析确定单倍型块。通过针对潜在混杂因素进行调整的无条件逻辑回归模型评估关联。我们发现CYP19A1基因型和单倍型与子宫内膜癌风险之间无显著关联。然而，在体重指数（BMI）>23的女性中，rs2899473、rs1865803、rs16964220、rs2008691、rs17647707、rs17647719、rs1902586、rs936306和rs1004982呈现显著正相关，而rs1902585、rs752760和rs2445768呈现负相关。这些显示与BMI存在显著交互作用。此外，在确定的六个单倍型块中，第1块的单倍型CTT、第5块的GATA和第6块的CA与BMI存在统计学显著交互作用。这些结果表明，CYP19A1基因多态性可能在子宫内膜癌的病因学中起重要作用，并且这些多态性的作用可能受BMI影响。
