Obesity Factors May Increase Kidney Cancer Risk

Specific risk factors related to obesity may increase a person’s chance of developing renal cell carcinoma (RCC) — a common type of kidney cancer – according to recent research conducted at Spectrum Health.

Using large-scale, genome-wide associated studies, the researchers identified genetic variants associated with obesity measures, including blood pressure, lipids, type 2 diabetes, insulin and glucose. These factors were evaluated for their relationship to kidney cancer (if any) in 10,000 patients with the disease compared to 20,000 control patients.

Diastolic blood pressure (the pressure in your blood vessels when your heart rests between beats) and fasting insulin (an indication of insulin resistance) were both associated with kidney cancer risk, while there was little evidence for the relationship between kidney cancer and systolic blood pressure (the pressure in your blood vessels when your heart beats), circulating lipids, overall diabetes and fasting glucose (how much glucose is in a blood sample after an overnight fasting).

“Prior observational studies identified putative risk factors that increased the risk of renal cell carcinoma (RCC), including obesity and other obesity-related factors,” study author Brian Lane, M.D., Ph.D., a board-certified urologist and Betz Family Endowed Chair for Cancer Research at Spectrum Health said in an interview with CURE. “Traditional observational studies have limitations, so that it is impossible to determine which obesity-related risk factors directly influence RCC risk.”

These findings are important because, according to the National Cancer Institute, kidney and renal pelvis cancer is the eighth most common cancer type in the country and makes up about 3.8 percent of all new cancer cases. In 2018, there were more than 65,000 new diagnoses and nearly 15,000 people died from the disease.

Lane mentioned that this particular study used a different methodology — called mendelian randomization – that, “circumvents many of the inherent limitations of traditional observational studies by using genetic proxies of putative risk factors.” However, these are not subject to reverse causation and are less likely to be confounded by other risk factors, he added.

Despite the reliability of these findings, Lane said that researchers are still unsure about why diastolic blood pressure — and not systolic blood pressure – would be an important factor in RCC.

When it comes to insulin, he explained that insulin resistance can lead to compensatory hyperinsulinemia (where there is an abundance of insulin in the blood stream, relative to the amount of glucose) when pancreatic beta cells increase insulin secretion to regulate blood glucose. “The contrasting associations with risk for the beta-cell dysfunction and insulin-resistance (single nucleotide polymorphisms) would therefore lend further support for a role of insulin in RCC etiology, as well as explain the lack of association with RCC risk for overall type 2 diabetes,” Lane said.

There are still some unanswered questions in this line of research, but for now, Lane said that these findings should act as a motivator for individuals to keep their weight in balance. “One clear way to reduce the risk of developing kidney cancer is by management of (and avoidance of) obesity.”