Aberrant promoter methylation of p15 INK4b and p16 INK4a genes may contribute to the pathogenesis of multiple myeloma: a meta-analysis

We carried out the current meta-analysis aiming to comprehensively assess the potential role of p15 (INK4b) and p16 (INK4a) aberrant promoter methylation in the pathogenesis of multiple myeloma (MM). The MEDLINE (1966 2013), Cochrane Library (Issue 12, 2013), EMBASE (1980 2013), CINAHL (1982 2013), Web of Science (1945 2013), and Chinese Biomedical (CBM) (1982 2013) databases were searched without language restrictions. Meta-analyses were conducted using Stata software (Version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and their 95 % confidence intervals (95 %CIs) were calculated. Thirteen clinical case-control studies, which enrolled a total of 465 MM patients and 180 healthy subjects, were included in the meta-analysis. The results of our meta-analysis demonstrated that the frequencies of p15 (INK4b) and p16 (INK4a) promoter methylation in cancer samples were significantly higher than in normal samples (p15 (INK4b) : OR = 6.26, 95 %CI = 3.87 10.12, P < 0.001; p16 (INK4a) : OR = 2.26, 95 %CI = 1.22 4.20, P < 0.001). Ethnicity-stratified analysis showed that the aberrant methylation of p15 (INK4b) was significantly related with the risk of MM among both Caucasians and Asians (all P < 0.05). Furthermore, our results also illustrated a strong positive correlation between p16 (INK4a) promoter methylation and the pathogenesis of MM among Asians (OR = 5.17, 95 %CI = 3.45 7.74, P < 0.001), but not among Caucasians (P > 0.05). The current meta-analysis confirms and reinforces existing findings that p15 (INK4b) and p16 (INK4a) promoter methylation may be closely implicated in the pathogenesis of MM.