title: Aberrant promoter methylation of p15 (INK⁴b) and p16 (INK⁴a) genes may contribute to the pathogenesis of multiple myeloma: a meta-analysis.
abstract: 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.
authors.affiliation: Department of Hematology, Affiliated Hospital of Beihua University, Liberation Road No. 12, Jilin, 132011, People's Republic of China, wangxuanwx321@126.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Zhu
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Cui
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Yu
mesh_terms: D044466:Asian People / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D009101:Multiple Myeloma / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16