Dataset Information

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.

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 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. 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.

SUBMITTER: Wu H

PROVIDER: S-EPMC3472165 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.

Wu Huanlei H Xu Li L Chen Jigui J Hu Junbo J Yu Shiying S Hu Guangyuan G Huang Liu L Chen Xiaoping X Yuan Xianglin X Li Guojun G

BMC cancer 20120703

<h4>Background</h4>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 ...[more]

PMID: 22759347

Similar Datasets

Project description:ImportanceHalf of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention.ObjectiveTo compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal.Design, setting, and participantsThis is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022.InterventionsParticipants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks.Main outcomes and measuresIn this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics.ResultsA total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.Trial registrationClinicalTrials.gov Identifier: NCT02516202.

Dataset Information

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.

Publications

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets