Association Between Polymorphisms of NRF2 and Breast Cancer Risk in Japanese Population

The nuclear factor (erythroid-derived 2)-like 2 gene (NRF2) plays important roles in cellular defense, tumor suppression, and oncogenesis. However, little information is available on the polymorphisms of NRF2 and their clinical relevance. We aimed to investigate the relationship between NRF2 and breast cancer risk. We developed a rapid genetic testing method for the detection of a single-nucleotide polymorphism (SNP) (c.‒617C>A) in the antioxidant response element-like loci of human NRF2 that is involved in the antioxidation effect. One hundred forty-six breast cancer patients and 101 controls were enrolled in this study. The genotype distributions in controls were 88 for CC/CA (87%) and 13 for AA (13%). In contrast, those in breast cancer patients were 138 for CC/CA (95%) and 8 for AA (5%). The genotype distributions in breast cancer patients differed significantly from those in controls (P<0.040, adjusted OR=2.55; 95%CI: 1.02‒6.40). The SNP is not associated with the expression levels of HO‒1 and CYP2A6 or the survival of breast cancer patients. These results suggest that this SNP of human NRF2 is a potential biomarker for breast cancer susceptibility.