Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.
Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.
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雌激素受体β变异和血清雌二醇水平与结直肠癌风险的关联：病例对照研究
DOI：
10.1186/1471-2407-12-276
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发表时间：
2012-07-03
期刊：
影响因子：
3.8
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Wu H;Xu L;Chen J;Hu J;Yu S;Hu G;Huang L;Chen X;Yuan X;Li G
内源性雌激素可能在结直肠肿瘤发生中起重要作用。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表达缺失已被表明是结直肠癌（CRC）发展过程中的一个常见步骤。流行病学研究已揭示雌激素受体β（ESR2）的几种功能性多态性与癌症风险相关，但在结直肠癌中的相关研究有限，尤其是在男性中。本研究旨在探讨男性循环雌二醇及ESR2变异与结直肠癌风险的关联。
我们开展了一项病例对照研究，仅纳入390例男性结直肠癌患者和445例健康男性对照。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。采用多变量逻辑回归模型评估这些变量与结直肠癌风险之间的关联。
ESR2 rs1256049的CT/TT基因型与结直肠癌风险降低相关（比值比[OR]，0.7；95%置信区间[CI]，0.5 - 1.0），而rs4986938的CT/TT基因型与结直肠癌风险增加相关（OR，1.5；95%CI，1.0 - 2.1）。此外，这两个SNP的风险基因型数量增加时，结直肠癌风险呈剂量 - 反应关系增加（趋势P值，0.003）。具体而言，同时携带这两个SNP风险基因型的受试者患结直肠癌的风险最高（OR，2.0；95%CI，1.3 - 3.3）。此外，男性血清雌二醇浓度单独与结直肠癌风险相关（OR，1.2；95%CI，1.0 - 1.3）。然而，与具有rs4986938的CC基因型且血清雌二醇水平低的个体相比，同时具有rs4986938的CT/TT基因型且血清雌二醇水平高的个体患结直肠癌的风险较高（OR，2.3；95%CI，1.4 - 3.9）。对于SNP rs1256049未观察到类似的联合结果。
这些结果表明，内源性雌激素和ESR2的基因变异可能单独或更有可能共同影响中国汉族男性人群的结直肠癌风险，但需要更大规模的研究来验证我们的发现。
Background
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.
Methods
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.
Results
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 (P
trend
, 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.
Conclusions
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.
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影响因子：
8.8
作者：
Silva, ID;Swerdlow, AJ
通讯作者：
Swerdlow, AJ
绝经后内源性激素水平和结直肠癌的风险。
DOI：
10.1158/1055-9965.epi-08-0777
发表时间：
2009-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Clendenen TV;Koenig KL;Shore RE;Levitz M;Arslan AA;Zeleniuch-Jacquotte A
通讯作者：
Zeleniuch-Jacquotte A
DOI：
10.1097/01.gme.0000182804.14385.a2
发表时间：
2006-05-01
影响因子：
2.7
作者：
Silvestri, Sandra;Thomsen, Anne Bloch;Brandi, Maria Luisa
通讯作者：
Brandi, Maria Luisa
DOI：
10.1093/jnci/87.7.517
发表时间：
1995-04-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
CALLE, EE;MIRACLEMCMAHILL, HL;HEATH, CW
通讯作者：
HEATH, CW
影响因子：
158.5
作者：
Chlebowski, RT;Wactawski-Wende, J;Carleton, R
通讯作者：
Carleton, R