Oxidative stress and gender disparity in cancer

Abstract

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.

Keywords:

• Oxidative stress
• ROS
• gender disparity
• cancer
• sex hormone

Disclosure statement

The author reports no conflict of interest.

Additional information

Funding

This research was supported by Duksung Women’s University Research Grants 2019.