Gene Regulation of Leptin Receptors Appear Linked to Kidney Cancer in People with Obesity, Study Reports

Gene Regulation of Leptin Receptors Appear Linked to Kidney Cancer in People with Obesity, Study Reports

Researchers identified a possible molecular link between obesity and kidney cancer. The findings, presented at the American Association of Cancer Research (AACR) Annual Meeting in New Orleans, showed that hypermethylation of leptin receptors might be tied to the recurrence of renal cell carcinoma, and help to explain previously observed associations of increased kidney cancer risk in obese people.

Researchers at the University of Texas MD Anderson Cancer Center were studying patients with renal cell carcinoma, the most common kind of kidney cancer, when they discovered that leptin receptors, called LEPR, were hypermethylated. Methylation, the adding of chemical moieties called methyl groups, is a common way to control gene expression, and many genes involved in cancer are regulated by this mechanism.

“Obesity is an established risk factor for renal cell carcinoma, with more than 40 percent of these cases attributed to excessive body weight,” Xifeng Wu, professor of Epidemiology and principal study investigator, said in an MD Anderson news release. “Growing evidence suggests that obesity also may be associated with the prognosis of renal cell carcinoma. The molecular mechanism LEPR and two other genes, NPY and LEP, are involved in renal cell carcinoma tumorigenesis. LEPR methylation in tumors is associated with recurrence in renal cell carcinoma patients, and thus, LEPR may provide a functional link between obesity and renal cell carcinoma.”

The team looked into methylation levels in 20 obesity-associated genes, exploring a possible correlation to cancer. Researchers compared a total of 240 pairs of tumor tissue with adjacent healthy tissue from newly diagnosed kidney cancer patients.

Adjusting the analysis for a multitude of factors that might influence a possible association, they found that methylation of LEPR was associated with a number of poor outcomes.

Julia Mendoza-Perez, a visiting scientist of Epidemiology at MD Anderson who presented the findings at AACR, said, “Patients were classified into high- and low-LEPR methylation groups. We found that high LEPR methylation was associated with a significantly higher risk of tumor recurrence.”

“In addition, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade, and clear cell renal cell carcinoma histology,” Dr. Wu added.

The researchers concluded that, in order to understand how leptin receptors influence cancer, the effects of methylation of LEPR need further studies.

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