Manganese superoxide dismutase polymorphism treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer

摘要

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene SOD2 and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial (SWOG 8897), we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3–4 neutropenia (OR=0.52, 95% CI=0.29–0.92) but had worse DFS (HR=1.59, 95% CI=0.99–2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress-related enzymes on cancer treatment toxicity and efficacy.