Obesity usually shortens our lifespan, but a new U.S. study published Monday found that overweight patients with advanced kidney cancer had significantly longer survival than those who were normal or underweight.
Having a high body mass index (BMI) is a well-established risk factor for clear cell renal cell carcinoma, the most common type of kidney cancer. BMI is the ratio of weight in kilograms divided by the squared height in meters.
The new study published in the Journal of Clinical Oncology involving about 7,000 patients in four databases, however, showed that when overweight individuals developed kidney cancer -- especially in its advanced, metastatic form -- their disease progressed more slowly and they lived longer than their normal-weight counterparts.
In one group of nearly 2,000 patients, the median overall survival of patients with high BMI was 25.6 months compared to 17.1 months for patients with low BMI.
The mortality rate for the overweight cancer patients was 16 percent less over the course of the study, which began in 2003.
The report's authors, led by senior and corresponding author Toni Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, noted previous research showed that kidney cancer diagnosed in obese patients had less-dangerous pathological characteristics, and when treated with targeted therapies, these patients, even when their disease had spread, had better overall survival.
To explain that, they searched for molecular differences between the high- and low-BMI patients in two of the databases, but didn't reveal any differences in the tumors' DNA, such as gene mutations, that might account for the disparity.
But when the scientists looked at gene expression, the rate at which genetic information was being used by the cell to make proteins, they spotted a difference related to a gene called fatty acid synthase (FASN).
Overexpression of FASN, known as a metabolic oncogene, has previously been found in many types of cancer, and the new study showed expression of FASN was decreased in patients with high BMI compared to normal weight patients.
Why FASN is downregulated in obese patients isn't yet known, but the authors of the study said the results provide a rationale for experiments aimed at inhibiting FASN expression in kidney cancer patients -- regardless of their BMI -- in an effort to improve outcomes.
FASN inhibitors, including some derived from natural products, have been in development for several years and are considered a promising approach to cancer treatment.
"We plan to test FASN inhibitors in an animal model as a possible therapy for kidney cancer," said Choueiri.
