New research shows that tumors found in obese patients may be more indolent than those in nonobese patients, and this may, in part, be related to alterations in fatty acid metabolism explaining the obesity paradox in clear-cell renal cell carcinoma.
Body mass index was not an independent prognostic factor for cancer-specific mortality in patients with renal cell carcinoma, despite the appearance of an increased survival among obese patients compared with nonobese patients.
Instead, new research showed that tumors found in obese patients may be more indolent than those in nonobese patients, and this may, in part, be related to alterations in fatty acid metabolism explaining the obesity paradox in clear-cell renal cell carcinoma.
“Our study in no way is suggesting that patients with kidney cancer gain weight to help them fight the disease,” said study author A. Ari Hakimi, MD, of the department of surgery at Memorial Sloan-Kettering Cancer Center. “Rather, the study implicates a possible interaction between the altered hormonal milieu of obese patients and the intrinsic tumor biology. The notion that the body and the tumor can interact in ways that can modulate tumor behavior is intriguing and opens up a new area of research and potential therapies.”
Hakimi and colleagues performed a large and rigorous analysis of the relationship between obesity and clear-cell renal cell carcinoma in terms of tumor characteristics and clinical outcomes. They examined data from 2,119 patients with clear-cell renal cell carcinoma who underwent renal mass surgery at Memorial Sloan-Kettering Cancer Center from 1995 to 2012. The analysis looked for an association between BMI and advanced disease and took into account potential confounding factors that obese patients might have. The results of the study were published in the Journal of the National Cancer Institute.
“We were able to validate previous work that showed that obese patient appear to have less aggressive tumors compared to patients of normal body habitus,” Hakimi said. “Further, we demonstrated that this was not likely due to a bias of earlier detection or co-morbidities, which might lead to more frequent imaging as we controlled for these factors in the analysis.”
Of the study population, 19.8% of patients were classified as normal weight, 38% as overweight, and 42.1% as obese. Results of the study indicated that obese or overweight patients were less likely to present with advanced disease compared with nonobese counterparts (OR = 0.61; 95% CI, 0.48-0.79 for obese and OR = 0.65; 95% CI, 0.51-0.83 for overweight).
In a univariate analysis, BMI was found to have an inverse association with a higher cancer-specific mortality (P = .005). When a multivariate analysis adjusted for demographics and relevant confounders, the association between BMI and cancer-specific mortality remained statistically significant. However, when the analysis adjusted for stage and grade the association lost its significance.
“Finally, we performed genomic analysis on a subset of patients and showed that metabolic genes related to fat metabolism were altered in patients with higher BMI which might account for their less aggressive tumors,” Hakimi said.
Specifically, fatty acid synthase was upregulated in the normal BMI group and was downregulated in the obese group. Further analysis revealed that upregulation of fatty acid synthase was associated with an increased incidence of cancer-specific death (P < .001).
“Collectively our results suggest that the decreased mortality observed among obese clear-cell renal cell carcinoma patients may not merely be explained by detection bias or weight loss but that tumors developing in obese patients may be more indolent than those in normal-weight patients,” the researchers wrote.