Obesity Linked With Increased Risk of Certain Subtypes of RCC

A nested case-control study found that the association between obesity and RCC varies depending on subtype.

The association found between obesity and renal cell carcinoma (RCC) varies by subtype, according to the results of a nested case-control study and meta-analysis.

“Our results provide the strongest evidence to date that the association between obesity and RCC differs by subtype, with obese individuals at increased risk of clear cell and chromophobe RCC, compared to normal weight individuals,” Catherine L. Callahan, PhD, of the National Cancer Institute, told Cancer Network. “Our findings underscore the importance of maintaining a normal weight as a strategy for the prevention of most types of kidney cancer, among many other diseases.”

According to Callahan, understanding of the causes of kidney cancer has broadened greatly in the last 15 years. Previously, RCC was studied as a single malignancy, but it is now recognized as many different subtypes with potentially distinct causes.

“To advance our understanding in this area, we conducted a study investigating risk factors for the three most common RCC subtypes, clear cell (making up 70%–75% of all cases), papillary (5%–15%), and chromophobe (3%–5%),” Callahan said.

First, Callahan and colleagues conducted a nested case-control study of 685 cases from the Kaiser Permanente Northern California (KPNC) healthcare network. The patient pool included 421 patients with clear cell subtype, 65 with papillary, 24 with chromophobe, 35 with other, 141 with not otherwise specified, and 4,266 controls. The researchers evaluated whether there was an association between obesity and RCC subtype. The results were published in Cancer Epidemiology.

Among the KPNC patients, a body mass index (BMI) of 30 or greater was associated with a 50% increased risk of clear cell RCC (odds ratio [OR], 1.5; 95% CI, 1.1–2.1) and a more than two times increased risk for chromophobe RCC (OR, 2.5; 95% CI, 0.8–8.1) compared with patients with a BMI of less than 25. However, there was no increased risk for papillary RCC (OR, 1.0; 95% CI, 0.5–1.9).

“The lack of an association with papillary RCC is important because it suggests that the relationship between obesity and kidney cancer risk is more complex than originally suspected,” Callahan said.

No differences between subtypes were found to be associated with smoking, hypertension, or chronic kidney disease. When cases were restricted to stage II or greater, the association between obesity and clear cell RCC persisted, but was not associated with papillary or chromophobe RCC.

The researchers also conducted a meta-analysis combining the results from KPNC and those from three other studies. These results were similar to the initial study. The summary relative risks (SRR) for obesity were increased for clear cell RCC (SRR, 1.8; 95% CI, 1.5–2.2) and chromophobe RCC (SRR, 2.2; 95% CI, 1.3–3.7), but not for papillary (SRR, 1.2; 95% CI, 0.8–1.6).

“The obesity epidemic in the US has numerous adverse health outcomes, including clear cell and chromophobe RCC,” Callahan said. “Losing weight has many benefits, including reduced risk for these cancers.”