Thymidylate Synthase Confounding Issues

As previously noted, difference in MTX dosing may confound associations between the 28 bp insertion and the clinical endpoints of interest. Likewise, biases in case ascertainment may also make interpretation of the studies more difficult. Relling et al. note this concern given the different indications for osteonecrosis screening used in Total Therapy XIIIB and XIV trials (22). Finally, the limited sample size of the Lauten et al. report makes interpretation of the reported negative result difficult (21).

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