Previously we have reported that the human population located near the Semipalatinsk nuclear test site exhibited significantly enhanced levels of minisatellite mutations (MM), indicating an increased germ-line mutation rates from the exposure in 3 generations. It was assumed that the MM may potentially be used as a biomarker for monitoring functional genetic alterations. In this study, the influence of polymorphisms in genes on the expression of MM in the same two populations, and their relationships with radiation exposure were studied. Three polymorphic DNA - repair genes (XRCC1 Arg194Trp, XRCC1 Arg399Glu, and XRCC3 Thr241Met) and two xenobiotic detoxification genes (GST and GSTM1) were selected for analyses. The functionally active XRCC1 Arg194Trp was significantly linked to low MM and over-represented in the exposed in comparison with the control populations. Both GSTT1 and GSTM1 nulls were significantly associated with increased MM.ere. The former was under-represented but the latter was significantly over-represented in the exposed in comparison with the control populations. In summary, the data indicates that the expected enzymatic functions of the polymorphic genes are consistent with the MM expression, except the XRCC1 Arg399Glu variant gene. Moreover, the variant genes were retained in the three generations in association with their useful function, except for the GSTM1 null.