Abstract 2634: Prognostic value of obesity-related genes methylation in localized renal cell carcinoma patients

Obesity is an established risk factor for renal cell carcinoma (RCC): more than 40% of RCC cases in US are attributed to excessive body weight. Growing evidence suggests that obesity may also be associated with the prognosis of RCC. The molecular mechanism linking obesity and RCC is not well understood. In the present study, we evaluated the association between promoter CpG island methylation of 20 obesity-related genes and RCC. A total of 275 newly diagnosed and previously untreated Caucasian RCC patients were included. For the discovery population, 75 tissue pairs of RCC tumors and normal adjacent tissues from the surrounding kidney were used and for the validation population an additional 200 pairs were included. Pyrosequencing was used to determine CpG site methylation on bisulfite-treated genomic DNA. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confident intervals (CIs) for the association of CpG methylation with recurrence and Kaplan-Meier curve to plot disease free survival (DFS) time by different CpG site methylation. The average age of the patients was 59 years and they were largely males; ∼50% were never smokers. Most of the cases were clear cell RCC (ccRCC) and clinical stage I. Among the 20 markers, LEP, LEPR and NPY were significantly hypermethylated in tumor tissues compared to normal tissues (p