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-β (ER-β) 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.