Circulating levels of obesity-related markers and risk of renal cell carcinoma in the PLCO cancer screening trial

Abstract

Purpose Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, although recent evidence suggests that the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines may play a role. Methods To address this question we conducted a nested case-control study of RCC (252 cases, 252 controls) within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial investigating associations with pre-diagnostic serum levels of total adiponectin, high-molecular- weight (HMW) adiponectin, IGF-1, IGF binding protein-3 (IGFBP-3), and C-peptide. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated using conditional logistic regression. Results After adjustment for potential confounders, non-significant associations with RCC were observed for total adiponectin (OR for highest vs. lowest quartile = 0.65, 95% CI 0.37–1.14; Ptrend=0.35), HMW adiponectin (0.67, 0.38–1.17; Ptrend=0.36), IGF-1 (1.35, 0.77–2.39; Ptrend=0.17), IGFBP-3 (1.47, 0.83–2.62; Ptrend=0.53), and C-peptide (1.52, 0.86–2.70; Ptrend=0.15). In a joint analysis with body mass index (BMI, kg/m2), obese individuals (BMI ≥30) with above- median levels of IGFBP-3 had a significantly higher risk vs. those with BMI <25 and below- median IGFBP-3 (OR 2.42, 1.11–5.26), whereas obese individuals with low IGFBP-3 did not (1.18-=0.53–2.64) (Pinteraction=0.35). Conclusions The results of this study, while not clearly supporting associations with these obesity-related hormones, suggest that the association between obesity and RCC may be partially modified through mechanisms related to elevated IGFBP-3.

Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis

“…Of them, 11 were further excluded because 3 of them reported overall cancer risk rather than RCC risk; 1 reported cancer mortality rather than RCC risk; 2 did not measure circulating adiponectin; 2 were reports of the same cohorts; and the other 3 did not include control groups of healthy participants. Finally, 8 studies [14][15][16][17][18][19][20][21] were included.…”

“…In a few pilot studies, lower circulating adiponectin was observed in RCC cases than in healthy controls, [14][15][16][17] while no significant difference of circulating adiponectin was observed between RCC cases and controls in some other studies. [18][19][20][21] The inconsistency of these findings may be explained by the differences of study population and sample sizes of the studies. A previous meta-analysis by Yap et al 22 included seven studies [14][15][16][18][19][20][21] and concluded that patients with RCC had lower circulating adiponectin than healthy controls.…”

“…[18][19][20][21] The inconsistency of these findings may be explained by the differences of study population and sample sizes of the studies. A previous meta-analysis by Yap et al 22 included seven studies [14][15][16][18][19][20][21] and concluded that patients with RCC had lower circulating adiponectin than healthy controls. However, a recently published study was not included.…”

A Functional Interplay between IGF-1 and Adiponectin

“…Circulating IGF-1, adiponectin, and others (IGFBP-3, HMW adiponectin) were also investigated in relation to renal cell carcinoma (RCC) risk, in a prospective study within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trials (a population-based multi-center randomized screening trials in the US) [ 127 ]. Data, however, did not provide definite evidence of the starting hypothesis, although the authors observed a weak association between adiponectin and IGFBP-3.…”

“…Data, however, did not provide definite evidence of the starting hypothesis, although the authors observed a weak association between adiponectin and IGFBP-3. In particular, high adiponectin and HMW adiponectin levels were related to a reduced RCC risk; on the contrary, high IGF-1 and IGFBP-3 levels suggestively increased RCC risk [ 127 ].…”