As the different results obtained among the included studies could be attributable to population differences in Arg399Gln mutation frequency or linkage disequilibrium block, subgroup analysis according to race was conducted. In the Caucasian and Asian subgroups, heterogeneity was not found to be large (I2<50%) under any contrast model. Therefore, the fixed-effects model was used in Caucasian and Asian subgroups under any contrast model. The Arg399Gln SNP was then found to significantly increase the risk of childhood ALL only among Asians, under the dominant (OR 2.11, 95% CI 1.50–2.97, P<0.0001; Figure 4B), allele contrast (OR 1.72, 95% CI 1.33–2.23, P<0.0001; Figure 4C), and homozygote contrast (OR 2.34, 95% CI 1.25–4.36, P=0.008; Figure 4D) models. No association was observed under the recessive model (OR 1.70, 95% CI 0.94–3.08, P=0.08; Figure 4A). Furthermore, no association between the XRCC1 Arg399Gln SNP and risk of childhood ALL was found under any contrast model among Caucasian or mixed-race populations (Figure 4).


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(To enlarge portions of Figure 4, click on the figure.)

CML

CML was surveyed in two studies, involving data from 338 cases and 406 controls, all of whom were Caucasian. No heterogeneity was found between the two included studies under any contrast model, and so the fixed-effects model was used. Overall, the meta-analysis for those studies revealed no association between the XRCC1 Arg399Gln SNP and risk of CML under any contrast model (Table 2).

CLL

The association between the XRCC1 Arg399Gln SNP and risk of CLL was researched in three studies with 712 cases and 614 controls, all of whom were Caucasian. The forest plot revealed a high degree of heterogeneity. Random-effects modeling was thus performed for the four contrast models. The meta-analysis for these studies revealed no association between the SNP and risk of CLL under any contrast model.

In view of such a high degree of heterogeneity, a sensitivity analysis was conducted, revealing the study of Duman et al23 as an outlier. Removal of that data from the analysis reduced the heterogeneity under all of the four contrast models.

Meta-analysis using fixed-effects model for the remaining two studies revealed no association between the SNP and risk of CLL under any contrast model (Table 2). Therefore, it indicates that the result about CLL is insensitive to the study of Duman et al.23