Association Between the Individual and Combined Effects of the and Polymorphisms and Risk of Leukemia: A Meta-Analysis.

Fourteen meta-analyses reported the individual effects of the and polymorphisms on leukemia risk. However, over 40 studies were not included in previously published meta-analyses. Moreover, one key aspect was that previous meta-analyses did not conduct the false-positive test on the aforementioned issues. Furthermore, previous meta-analyses did not observe the combined effects of present/null and present/null polymorphism with leukemia risk. Therefore, we conducted the current study to further analyze these associations. This study aimed to investigate the association between the individual and combined effects of the present/null and present/null polymorphisms and the risk of leukemia. A meta-analysis was performed applying Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Moreover, false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP) were applied to investigate the false-positive results. The individual and null genotypes and combined effects of the two genes were associated with a significantly increased leukemia risk in overall and several subgroup analyses, such as Asians, Caucasians, and so on. Then, further analysis was conducted using FPRP and BFDP. Significant associations were considered as "positive" results on the null genotype with leukemia risk in overall populations (FPRP < 0.001 and BFDP = 0.006), Asians (FPRP < 0.001 and BFDP < 0.001), and East Asian population (FPRP < 0.001 and BFDP = 0.002). For the null genotype, significant associations were regarded "positive" results in overall populations, acute myeloid leukemia (AML), Asians, and East Asian population. For the combined effects of the and polymorphisms, significant associations were also considered "positive" results in the overall analysis of Asians, Indians, and East Asian population. This study strongly indicates that the individual and null genotypes and combined effects of the two genes are associated with increased leukemia risk in Asians, especially in the East Asian population; the null genotype is associated with increased AML risk; the combined effects of the two genes are associated with increased leukemia risk in Indians.