In this paper we evaluated the effects of polymorphisms in encoding genes for enzymes involved in DNA repair and in protection from ROS (reactive oxygen species), in relation to acute skin side effects of RT. In particular, the following polymorphic genes are involved in oxidative stress-related mechanisms (GSTs) and in DNA repair were taken into consideration: XRCC1(Arg399Gln/Arg194Trp), XRCC3(A4541G-5'UTR /Thr241Met), GSTP1(Ile105Val), GSTA1 and RAD51(untranslated region), which are involved in oxidative stress-related mechanisms (GSTs) and in DNA repair.
A statistically significant positive connection was found between the ≥G1 erythema and wt XRCC1 Arg194Trp, confirming the trend reported by Chang-Claude J et al. . Likewise, an association between XRCC1 Arg194Trp and skin reactions was also been described by Mangoni M. et al. . Also in our study, the wt XRCC3 Thr241Met showed a trend for having a protective role towards of erythema, according to data reported by Popanda et al.  and Mangoni M. et al. .
It is worthy to note that, Cecchin et al.  investigated the role of XRCC3A4541G-5'UTR, a non-coding polymorphism in the 5'UTR of the gene with an un-clarified effect on protein expression, in rectal cancer patients. The Authors suggested a protective role of the variant allele XRCC3A4541G-5'UTR toward radiation injury. It is important to stress that a statistically significant positive association correspondence was found between ≥G1 erythema and wt/het XRCC3A4541G-5'UTR also in our study, indicating the protective role of the variant allele towards radiation injury also regards to breast cancer. Whereas, no statistically significant correlation was found with other polymorphisms and erythema.
Due to the limited number of studies involving polymorphisms and also the limited number of toxic events reported in literature, a pooled analysis was performed for acute toxicity and was been shown as a Forest plot. This analysis has confirmed the role of some polymorphic variants as predictors of acute toxicity, although in many cases only as a trend (Figure 2).
We also performed tests to assess the association of different genes involved in developmental clinical radio-sensitivity. Particular, we tested whether there was a possible association between the variant mut/het of different genes.
The presence of the polymorphic variant mut/het of XRCC1 Arg194Trp or wt of XRCC1 Arg399Gln showed evidence of a protective role towards erythema. On the contrary, in the study by Mangoni et al.  the presence of XRCC1 Arg194Trp variant allele and XRCC1 Arg399Gln wt allele suggested a significant risk of toxicity induced by radiotherapy.
In the present study, a correlation was also found between the absence of erythema and the presence of a mut/het of XRCC1 Arg194Trp or of the wt XRCC3 Thr241Met, indicating the protective role of these alleles.
Further, the association of erythema with the presence of a mut/het of XRCC1 Arg194Trp or mut/het of GSTP1 was also found to be statistically significant indicating the protective role of these polymorphisms. In addition, a high rate of erythema was correlated with the mut/het of XRCC1 Arg194Trp or with of the wt GSTA1, while a trend toward having a protective factor was observed when a mut/het of XRCC1 Arg194Trp or the wt XRCC1 Arg399Gln alleles were expressed.