Genetics and Population Health Division, Queensland Institute of Medical Research, Herston, Brisbane, Queensland 4006, Australia.
Carcinogenesis. 2011 Mar;32(3):331-5. doi: 10.1093/carcin/bgq263. Epub 2010 Dec 10.
Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3' region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12-1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3' untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant.
长期、过度的雌激素暴露而无孕激素拮抗被广泛认为是子宫内膜癌发展的一个危险因素。孕激素的生理功能依赖于其受体[孕激素受体（PGR）]的存在，几项研究报道 PGR 基因中的单核苷酸多态性（SNP）与子宫内膜癌风险相关。我们试图证实先前报道的与子宫内膜癌风险相关的四种不同 PGR 多态性。最多有来自三个研究的 2888 例子宫内膜癌病例和 4483 例女性对照进行了四个 PGR 多态性（rs1042838、rs10895068、rs11224561 和 rs471767）的基因分型。采用调整年龄、研究、种族和体重指数的 logistic 回归计算比值比（OR）及其相关的 95%置信区间（CI）和 P 值。在所研究的四个 SNP 中，只有 PGR 基因 3'区域的 rs11224561 与子宫内膜癌风险显著相关。rs11224561 SNP 的 A 等位基因与子宫内膜癌风险增加相关（每个等位基因的 OR 为 1.31；95%CI 为 1.12-1.53，P = 0.001，调整年龄和研究），其作用的大小和方向与先前报道的一致。我们已经验证了先前在亚洲人群中报道的 PGR 3'非翻译区标记 SNP 与子宫内膜癌风险的关联。需要进行复制研究来细化风险估计，并确定这是或相关 SNP 是潜在的致病变异。
