Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
BMC Cancer. 2012 Jul 3;12:276. doi: 10.1186/1471-2407-12-276.
Endogenous estrogens may play a vital role in colorectal tumorigenesis. Estrogen receptor beta is the predominant subtype which mediates the biological effect of estrogens, while loss of expression of estrogen receptor beta has been indicated as a common step in the development of colorectal cancer (CRC). Epidemiological studies have revealed several functional polymorphisms of estrogen receptor beta (ESR2) for cancer risk, but relevant study in CRC is limited, particularly in men. This study aimed to investigate the association of circulating estradiol and variations of ESR2 with CRC risk in men.
We initiated a case-control study consisting of 390 patients with CRC and 445 healthy controls in men only. We genotyped ESR2 single nucleotide polymorphisms (SNPs) rs1256049 and rs4986938 and measured serum estradiol concentration using chemilluminescence immunoassay. Multivariable logistic regression model was performed to evaluate the associations between these variables and CRC risk.
ESR2 rs1256049 CT/TT genotypes were associated with reduced risk of CRC (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5-1.0), while rs4986938 CT/TT genotypes were associated with increased risk of CRC (OR, 1.5, 95% CI, 1.0-2.1). In addition, the CRC risk increased with the number of risk genotypes of these two SNPs in a dose-response manner (Ptrend, 0.003). Specifically, subjects carrying risk genotypes of both SNPs had the highest risk of CRC (OR, 2.0, 95% CI, 1.3-3.3.). Moreover, serum estradiol concentration alone was associated with risk of CRC in men (OR, 1.2, 95% CI, 1.0-1.3). However, individuals presenting both rs4986938 CT/TT genotypes and high level of serum estradiol had a high risk of CRC (OR, 2.3, 95% CI, 1.4-3.9), compared with those presenting CC genotype and low level of serum estradiol. The similar joint results were not observed for SNP rs1256049.
These results suggest that endogenous estrogen and genetic variations in ESR2 may individually, or more likely jointly, affect CRC risk in male Han Chinese population, while larger studies are needed to validate our findings.
内源性雌激素可能在结直肠肿瘤发生中发挥重要作用。雌激素受体β是介导雌激素生物学效应的主要亚型，而雌激素受体β的表达缺失已被认为是结直肠癌（CRC）发展的常见步骤。流行病学研究揭示了雌激素受体β（ESR2）的几种与癌症风险相关的功能多态性，但相关的 CRC 研究有限，尤其是在男性中。本研究旨在探讨循环雌二醇和 ESR2 变异与男性 CRC 风险的关系。
我们开展了一项仅在男性中进行的病例对照研究，共纳入 390 例 CRC 患者和 445 例健康对照。我们对 ESR2 单核苷酸多态性（SNP）rs1256049 和 rs4986938 进行基因分型，并使用化学发光免疫分析法测定血清雌二醇浓度。采用多变量 logistic 回归模型评估这些变量与 CRC 风险之间的关系。
ESR2 rs1256049 CT/TT 基因型与 CRC 风险降低相关（比值比 [OR]，0.7，95%置信区间 [CI]，0.5-1.0），而 rs4986938 CT/TT 基因型与 CRC 风险增加相关（OR，1.5，95% CI，1.0-2.1）。此外，这两个 SNP 的风险基因型数量与 CRC 风险呈剂量反应关系（Ptrend，0.003）。具体而言，同时携带这两个 SNP 的风险基因型的个体 CRC 风险最高（OR，2.0，95% CI，1.3-3.3）。此外，血清雌二醇浓度单独与男性 CRC 风险相关（OR，1.2，95% CI，1.0-1.3）。然而，同时存在 rs4986938 CT/TT 基因型和高水平血清雌二醇的个体 CRC 风险较高（OR，2.3，95% CI，1.4-3.9），与同时存在 CC 基因型和低水平血清雌二醇的个体相比。未观察到 SNP rs1256049 的类似联合结果。
这些结果表明，内源性雌激素和 ESR2 中的遗传变异可能单独或更可能共同影响中国汉族男性的 CRC 风险，需要更大规模的研究来验证我们的发现。
