Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
Gynecol Oncol. 2010 May;117(2):255-9. doi: 10.1016/j.ygyno.2010.02.002. Epub 2010 Mar 2.
Together, steroidogenic acute regulator (StAR) and the cholesterol side chain cleavage enzyme (P450scc), which is encoded by CYP11A1, mediate the initial and rate-limiting step in steroidogenesis. Given the role of estrogens in endometrial carcinogenesis, we hypothesized that genetic variation in StAR and CYP11A1 genes may influence endometrial cancer risk.
We genotyped four CYP11A1 tagging single nucleotide polymorphisms (SNPs) and two StAR SNPs in endometrial cancer case-control studies nested within the Nurses' Health Study (553 cases and 1339 controls) and the Women's Health Study (137 cases and 411 controls). We calculated odds ratios and 95% confidence intervals using conditional and unconditional logistic regression adjusted for endometrial cancer risk factors to examine the association between SNPs/haplotypes and endometrial cancer.
We observed an increased risk for women carrying the variant allele for rs4555110 (odds ratio (OR)=1.3, 95% confidence interval (CI)=1.1-1.7), rs3825944 (OR=1.4, 95% CI=1.1-1.8), and rs7173655 (OR=1.3, 95% CI=1.0-1.7) CYP11A1 SNPs but no significant associations with CYP11A1 haplotypes. CYP11A1 SNPs were not predictive of plasma estradiol levels. We observed no associations between StAR SNPs and endometrial cancer risk.
Genetic variants in CYP11A1 may influence endometrial cancer risk or may be markers for causal variants elsewhere. Polymorphisms in StAR are not associated with endometrial cancer risk, but further research is needed.
固醇急性调节蛋白（StAR）和胆固醇侧链裂解酶（P450scc）共同介导类固醇生成的初始和限速步骤，P450scc 由 CYP11A1 编码。鉴于雌激素在子宫内膜癌发生中的作用，我们假设 StAR 和 CYP11A1 基因的遗传变异可能影响子宫内膜癌的风险。
我们在护士健康研究（553 例病例和 1339 例对照）和妇女健康研究（137 例病例和 411 例对照）的嵌套病例对照研究中对 CYP11A1 四个标签单核苷酸多态性（SNP）和两个 StAR SNP 进行了基因分型。我们使用条件和非条件逻辑回归计算了比值比和 95%置信区间，以调整子宫内膜癌危险因素来检验 SNP/单倍型与子宫内膜癌之间的关联。
我们发现，携带 CYP11A1 rs4555110（比值比（OR）=1.3，95%置信区间（CI）=1.1-1.7）、rs3825944（OR=1.4，95%CI=1.1-1.8）和 rs7173655（OR=1.3，95%CI=1.0-1.7）变异等位基因的女性患子宫内膜癌的风险增加，但与 CYP11A1 单倍型无显著相关性。CYP11A1 SNP 不能预测血浆雌二醇水平。我们没有观察到 StAR SNP 与子宫内膜癌风险之间的关联。
CYP11A1 中的遗传变异可能影响子宫内膜癌的风险，或者可能是其他地方的因果变异的标志物。StAR 中的多态性与子宫内膜癌风险无关，但需要进一步研究。
