Obesity associated with tumor indolence in renal cell carcinoma

Obese patients with renal cell carcinoma tended to have more indolent tumors than normal-weight patients, according to study results.

However, after researchers controlled for stage and grade, BMI was not an independent predictor of cancer-specific mortality.

The study included 2,119 patients with clear-cell renal cell carcinoma who underwent renal mass surgery at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. The median age of patients was 61 years. Most patients were men (66.4%) and non-Hispanic white (91.3%).

Researchers classified 19.8% of patients (n=420) as normal weight, 38% (n=806) as overweight and 42.1% (n=893) as obese.

Advanced-stage disease was less common in patients who were obese (OR=0.65; 95% CI, 0.51-0.83) and overweight (OR=0.61; 95% CI, 0.48-0.79) compared with normal-weight patients.

Results of univariable analyses indicated that higher BMI was associated with a reduced risk for cancer-specific mortality (P˂.005). However, this association was no longer statistically significant after researchers accounted for stage and grade (P˃.10).

Researchers conducted additional genomic analyses on 126 patients who participated in the Cancer Genome Atlas Project.

Fatty acid synthase (FASN) — which has been linked to aggressive disease and poor outcomes in several cancer types — was upregulated in patients with normal BMI and downregulated in patients with obesity.

Additionally, researchers found the upregulation of FASNwas significantly associated with increased cancer-specific mortality (P˂.001).

“Our findings suggest that although BMI is not an independent prognostic factor for cancer-specific mortality after controlling for stage and grade, tumors of obese patients may be more indolent than those of normal-weight patients, a pattern that is supported by alterations in gene expression signatures,” the researchers wrote. “Whether BMI’s contribution to FASN regulation is a cancer-specific phenomenon certainly requires further investigation, and our findings should be viewed as hypothesis-generating given the current paucity of mechanistic evidence.”

In an accompanying editorial, Lin Li and Kamyar Kalantar-Zadeh, MD, MPH, PhD, both of the Harold Simmons Center for Kidney Disease Research and Epidemiology in Orange, Calif., discussed the implications of the “obesity paradox” observed in this patient population.

“This study adds an important dimension to evidence supporting the obesity paradox in oncology in general and in kidney cancer in particular, as it is the first to examine the role of BMI and nutritional status in the severity of renal cell carcinoma and cancer survival while shedding some light into the biologic plausibility of the obesity paradox,” Li and Kalantar-Zadeh wrote. “Undoubtedly the impact of obesity in disease and health is not a simple black-and-white story. Such provocative findings … should not be considered as an attempt to undermine the legitimacy of an antiobesity campaign that is in the best interest of public health.”

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Disclosure: The researchers report consultant roles with and research funding from Aveo, Eisai, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer and Wilex AG.