Oxidative stress is caused by homeostasis disrupted by excessively increased
reactive oxygen species (ROS) due to intrinsic or extrinsic causes. Among diseases caused by the abnormal induction of ROS,
cancer is a representative disease that shows gender specificity in development and
malignancy. Females have the advantage of longer life expectancy than males because of the genetic advantages derived from X chromosomes, the
antioxidant protective function by
estrogen, and the decrease in exposure to extrinsic risk factors, such as alcohol and smoking. This study first examines the ordinary biological responses to oxidative stress and the effects of ROS on
cancer progression and describes the differences in
cancer incidence and mortality by gender and the differences in oxidative stress affected by
sex hormones. This paper summarized how several important
transcription factors regulate ROS-induced stress and in vivo responses, and how their expression is changed by
sex hormones.
Estrogen is associated with
disease resistance and greater mitochondrial function and reduces mitochondrial damage and ROS production in females than in males. In addition,
estrogen affects the activation of nuclear factor-erythroid 2 p45-related factor (NRF) 2 and the regulation of other
antioxidant-related
transcription factors through NRF2, leading to benefits in females. Because ROS have a variety of molecular targets in cells, effective
cancer treatment requires understanding the potential of ROS and focusing on the characteristics of the research target, such as the patient's gender. Therefore, this review intends to emphasize the necessity of discussing gender specificity as a new therapeutic approach for the efficient regulation of ROS considering individual specificity.