Synergistic action of folate intake and testosterone associated with breast cancer risk

The amount of irreparable DNA damage is a function of the rate of cell division, and the association between sex hormones and the risk of breast cancer has been explained by an increase in cell division. Folate intake insufficiency leads to disturbances in DNA replication and DNA repair. We hypothesized that folate intake insufficiency and high serum concentrations of sex hormones act synergistically on the risk of breast cancer. The aim of this study was to investigate the interaction between sex hormones (exposure of interest A) and dietary folate intake (exposure of interest B) on the risk of breast cancer. We included 342 breast cancer primary postmenopausal cases and 294 controls obtained from a large population-based case-control study. Multiple conditional logistic regression models were used for the analysis and interactions were tested. The joint effect of the lowest dietary folate intake (T1 < 259.40 mg/d) and the highest serum concentration of testosterone (T3 ≥ 0.410 on the risk of breast cancer was odds ratio = 9.18 (95% confidence interval 2.56-32.88) when compared to the lowest-risk category, namely, the group of women with the highest dietary folate intake (T3 > 381.29 mg/d) and the lowest serum concentration of testosterone (T1 ≤ 0.25 pg/mL). There were some indications that the estimated join effect was greater than the product of the estimated effects alone (P = .001). These findings have important public health implications with respect to reducing the risk of the most frequent cancer in women worldwide.