Obesity, high DBP up risk of renal cell carcinoma
Insulin plays an aetiological role in renal cell carcinoma (RCC), while obesity or having an elevated diastolic (DBP), but not systolic (SBP), blood pressure increases RCC risk, according to a recent study.
“[T]his study confirmed the important role of being overweight and having elevated DBP in affecting RCC risk and provided novel evidence for an aetiological role of elevated insulin,” researchers said.
Genetic markers linked to obesity measures, BP, lipids, type 2 diabetes (T2D), insulin and glucose were initially identified as instrumental variables. Their association with RCC risk was then assessed in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 controls in a two-sample Mendelian randomization (MR) framework. Researchers calculated odds ratios (OR) for a standard deviation increment in each factor to estimate the effect of RCC.
In the MR analysis, higher body mass index (BMI) elevated the risk of RCC (OR, 1.56; 95 percent CI, 1.44–1.70). Results were similar for waist-to-hip ratio (OR, 1.63; 1.40–1.90) and body fat percentage (OR, 1.66; 1.44–1.90). [PLoS Med 2019;16:e1002724]
Furthermore, higher fasting insulin (OR, 1.82; 1.30–2.55) and DBP (OR, 1.28; 1.11–1.47), but not SBP (OR, 0.98; 0.84–1.14), increased RCC risk. There was no association found for lipids, overall T2D or fasting glucose.
“There is an abundance of observational studies implicating obesity in RCC development, and several reviews have concluded that there is convincing evidence that being overweight or obese increases RCC risk,” according to researchers. [https://www.wcrf.org/sites/default/files/Kidney-cancer-report.pdf; N Engl J Med 2016;375:794-798]
An earlier MR analysis did not show a significant correlation between RCC and obesity, but the statistical power of that study was limited by its small sample size, they said. [Int J Epidemiol 2009;38:971-975]
There have been other obesity-related factors involved in RCC, specifically those traditionally associated with metabolic syndrome, defined as a cluster of factors that heighten the risk of T2D and cardiovascular disease, researchers noted. These risk factors include impaired glucose tolerance or diabetes, hypertension, and dyslipidaemia. [Arch Med Res 2005;36:2230-231; Nat Rev Urol 2010;7:245-257; Lancet 2010;375:181-183]
In the Metabolic Syndrome and Cancer consortium, individual-level prospective data were pooled from more than half a million participants. Its findings showed that men with high BMI, BP and blood triglycerides had a threefold risk increase in RCC compared with those without such conditions. In addition, these risk factors had independent effects on RCC risk. [Nat Rev Urol 2010;7:245-257; PLoS ONE 2013;8:e57475]
“We also note that the difference in risk effect estimates between the DBP and SBP was significant, suggesting that it was not due to chance and lack of statistical power,” researchers said. [PLoS ONE 2013;8:e57475; N Engl J Med 2000;343:1305-1311]
“The mechanisms by which elevated BP might influence RCC development are not established, but several plausible mechanisms have been suggested, including by influencing angiogenesis, growth factors, and renal function, thereby making the kidney more susceptible to carcinogens,” they added.