association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer a case control study协会的雌激素受体β变异和血清雌二醇水平与结直肠癌的风险一个病例对照研究.pdfVIP

Wu et al. BMC Cancer 2012, 12:276 /1471-2407/12/276 RESEARCH ARTICLE Open Access Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study 1† 4† 3 2 1 1 1 2* Huanlei Wu , Li Xu , Jigui Chen , Junbo Hu , Shiying Yu , Guangyuan Hu , Liu Huang , Xiaoping Chen , Xianglin Yuan1* and Guojun Li4,5 Abstract 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