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Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women.

ABSTRACT: The relationship between obesity and renal cell carcinoma (RCC) has been widely investigated. However, the effect of estrogen on this relationship in female RCC patients has not been evaluated. We conducted a case-control study to investigate the role of estrogen as a potential modifier of the association between obesity and RCC risk in Chinese women. A total of 497 consecutive female patients with pathologically confirmed RCC, including 364 clear cell RCC (ccRCC), were enrolled. Age-matched controls were selected from cancer-free females seeking physical examination in our institution. Estrogen receptor-? (ER-?) and insulin-like growth factor (IGF)-1 receptor (IGF-1R) expression levels were detected in RCC tissues. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression models. We observed a positive association between overweight and RCC risk in pre-menopausal but not post-menopausal women. Similar association was also observed between overweight and ccRCC risk. Overweight pre-menopausal women had an increased risk of RCC (OR: 1.67, 95%CI: 1.01-2.76), as well as an increased risk of ccRCC (OR: 1.73, 95%CI: 1.02-2.99), after adjusting for potential confounders. IGF-1R expression levels were higher in pre-menopausal compared with post-menopausal cases (P?=?0.015). These results suggest that estrogen plays an important role in RCC etiology and may modify the association between obesity and RCC risk in women. We hypothesize that estrogen may up-regulate IGF-1R and potentiate the deleterious effects of obesity-related elevations of insulin and IGFs.

SUBMITTER: Sun L

PROVIDER: S-EPMC6116349 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women.

Sun Lijiang L Chao Fan F Luo Bo B Ye Dingwei D Zhao Jun J Zhang Qiang Q Ma Xiaocheng X Zhang Guiming G

EBioMedicine 20180717

The relationship between obesity and renal cell carcinoma (RCC) has been widely investigated. However, the effect of estrogen on this relationship in female RCC patients has not been evaluated. We conducted a case-control study to investigate the role of estrogen as a potential modifier of the association between obesity and RCC risk in Chinese women. A total of 497 consecutive female patients with pathologically confirmed RCC, including 364 clear cell RCC (ccRCC), were enrolled. Age-matched con ...[more]

PMID: 30017803

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most lethal urologic cancer. Associations of both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with ccRCC have been reported, and underlying mechanisms of VAT perhaps distinguished from SAT, considering their different structures and functions. We performed this study to disclose different miRNA-mRNA networks of obesity-related ccRCC in VAT and SAT using datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA); and find out different RNAs correlated with the prognosis of ccRCC in VAT and SAT.MethodsWe screened out different expressed (DE) mRNAs and miRNAs of obesity, in both VAT and SAT from GEO datasets, and constructed miRNA-mRNA networks of obesity-related ccRCC. To evaluate the sensitivity and specificity of RNAs in networks of obesity-related ccRCC in both VAT and SAT, Receiver Operating Characteristic (ROC) analyses were conducted using TCGA datasets. Spearman correlation analyses were then performed to find out RNA pairs with inverse correlations. We also performed Cox regression analyses to estimate the association of all DE RNAs of obesity with the overall survival.Results136 and 185 DE mRNAs of obesity in VAT and SAT were found out. Combined with selected DE miRNAs, miRNA-mRNA networks of obesity-related ccRCC were constructed. By performing ROC analyses, RNAs with same trend as shown in networks and statistically significant ORs were selected to be paired. Three pairs were finally remained in Spearman correlation analyses, including hsa-miR-182&ATP2B2, hsa-miR-532&CDH2 in VAT, and hsa-miR-425&TFAP2B in SAT. Multivariable Cox regression analyses showed that several RNAs with statistically significant adjusted HRs remained consistent trends as shown in DE analyses of obesity. Risk score analyses using selected RNAs showed that the overall survival time of patients in the low-risk group was significantly longer than that in the high-risk group regardless of risk score models.ConclusionsWe found out different miRNA-mRNA regulatory networks of obesity-related ccRCC for both VAT and SAT; and several DE RNAs of obesity-related ccRCC were found to remain consistent performance in terms of ccRCC prognosis. Our findings could provide valuable evidence on the targeted therapy of obesity-related ccRCC.

Dataset Information

Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women.

Publications

Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women.

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