NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis

Abstract

Polymorphisms in NQO1, a gene coding for the phase II enzyme involved in the detoxification of quinone carcinogens, have been associated with childhood leukemia in some studies, although the observed direction and magnitude of effects have been inconsistent. Therefore, the authors systematically reviewed all published reports describing the effect of NQO1 in de novo childhood leukemia and conducted a meta-analysis of 7 case-control studies that examined the association between NQO1*2 and childhood leukemia. Although a family-based study previously demonstrated over-transmission of this allele among childhood acute lymphoblastic leukemia cases, the meta-analysis showed that the presence of a NQO1*2 variant allele, which reduces the activity of the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), had no significant effect on childhood leukemia. However, there was an increased risk associated with having at least 1 copy of the NQO1*2 allele in a subset of cases with MLL translocations (summary odds ratio = 1.39, 95% confidence interval: 0.98, 1.97). Heterogeneity between studies may be due to differences in population exposures to NQO1 substrates and small sample sizes, as well as potential population stratification in non-family-based studies. Therefore, further research is warranted on the role of NQO1 polymorphisms in the etiology of childhood leukemia, especially among MLL-positive leukemias.

Figures

Figure 1.

Process of article exclusion. MeSH, Medical Subject Headings; NQO1, NAD(P)H:quinone oxidoreductase 1.

Figure 2.

Forest plot of NQO1*2 and childhood acute lymphoblastic leukemia, random effects model. Test for heterogeneity: χ2 = 6.98, df = 4 (P = 0.14), I2 = 42.7%; test for overall effect: Z = 0.54 (P = 0.59). The odds ratio for each study is represented by a black square that is proportional to the sample size; the horizontal line shows the corresponding 95% confidence interval (CI). A dashed line marks the combined estimate, while the vertical solid line represents the null result.

Figure 3.

Forest plot of NQO1*2 and childhood acute myeloid leukemia, random effects model. Test for heterogeneity: χ2 = 4.00, df = 2 (P = 0.14), I2 = 50.0%; test for overall effect: Z = 0.36 (P = 0.72). The odds ratio for each study is represented by a black square that is proportional to the sample size; the horizontal line shows the corresponding 95% confidence interval (CI). A dashed line marks the combined estimate, while the vertical solid line represents the null result.

Figure 4.

Forest plot of NQO1*2 and MLL-positive leukemia (acute lymphoblastic leukemia or acute myeloid leukemia), fixed effects model. Test for heterogeneity: χ2 = 4.34, df = 3 (P = 0.23), I2 = 30.9%; test for overall effect: Z = 1.83 (P = 0.07). The odds ratio for each study is represented by a black square that is proportional to the sample size; the horizontal line shows the corresponding 95% confidence interval (CI). A dashed line marks the combined estimate, while the vertical solid line represents the null result.

Figure 5.

Forest plot of NQO1*2 and MLL-AF4 leukemia (acute lymphoblastic leukemia or acute myeloid leukemia), random effects model. Test for heterogeneity: χ2 = 11.98, df = 2 (P = 0.002), I2 = 83.3%; test for overall effect: Z = 0.88 (P = 0.38). The odds ratio for each study is represented by a black square that is proportional to the sample size; the horizontal line shows the corresponding 95% confidence interval (CI). A dashed line marks the combined estimate, while the vertical solid line represents the null result.