Combined effects of antioxidant vitamin and NOS3 genetic polymorphisms on breast cancer risk in women

It is becoming increasingly clear that there is wide heterogeneity in genetic predisposition to breast cancer and that breast cancer risk is determined by interactive effect between genetic and environmental factors.We investigated the combined effects of antioxidant vitamin intake and NOS3 genetic polymorphisms on breast cancer risk in a Korean population (Seoul Breast Cancer Study). Histologically confirmed breast cancer cases (n = 512) and age, menopause status-matched controls (n = 512) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 2001-2003. Two genetic polymorphisms of NOS3 (298G T and -786 T C) were assessed by single base extension assays.No overall association between the individual NOS3 genotypes or diplotypes and breast cancer risk was found, although the difference between cases and controls in the frequency of the NOS3 894 G T polymorphism showed borderline significance (OR = 0.74, 95% CI = 0.52-1.06). There was no significant difference in energy intake or the intake of antioxidant vitamins between cases and controls, with the exception of vitamin E (OR = 0.49 lowest vs. highest quartile, P(trend) 0.01). On the other hand, our results suggest that antioxidant vitamin intake may modify the effects of the NOS3 -786 T C or 894 G T genetic polymorphisms on breast cancer risk. Although a multiplicative interaction was not observed, the protective effect of β-carotene intake on breast cancer risk was observed predominantly in individuals with the TG:TG diplotype of NOS3 (OR = 0.68) but not observed with others diplotype. An inverse association between vitamin E intake and breast cancer risk was observed for individuals with the NOS3 786 TC + TT genotype and the NOS3 894 GG genotype. In addition, folic acid had a protective effect in the NOS3 786 TT and NOS3 894 GT + TT genotype.Our results suggest that intake of antioxidant vitamins might modify the association between genetic polymorphisms of NOS3 and breast cancer risk.