Clinical significance of p16(INK4A) and p14(ARF) promoter methylation in renal cell carcinoma: a meta-analysis

The inactivation of p16(INK4A) and p14(ARF) via promoter methylation has been investigated in various cancers. However, the clinical effects of p16(INK4A) and p14(ARF) promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16(INK4A) and p14(ARF) were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2.77, P = 0.005; OR = 11.73, P < 0.001, respectively). Methylated p16(INK4A) was significantly associated with the risk of RCC in the tissue subgroup, but not in the serum and urine subgroups. Methylated p16(INK4A) was significantly associated with tumor size. We did not find that p16(INK4A) promoter methylation was associated with sex, tumor grade, lymph node status, and tumor histology. Methylated p14(ARF) was significantly correlated with sex and tumor histology. Three studies reported that p16(INK4A) methylation was not significantly correlated with the prognosis of RCC. The results suggested that p16(INK4A) and p14(ARF) promoter methylation may be correlated with the carcinogenesis of RCC, and that methylated p14(ARF), especially, can be a major susceptibility gene. We also found the different clinicopathological significance of 16(INK4A) and p14(ARF) in RCC. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic effect of p16(INK4A) and p14(ARF) promoter methylation in RCC.