Sex-Dependent Differences in Colorectal Cancer: With a Focus on Obesity

Abstract

Colorectal cancer (CRC) is the third most common cancer and has the second highest cancer-related mortality in the world. The incident rates of CRC vary country-wise; however, population studies and data from different countries show a general increase in the CRC rate in young adults, males, and females ≥65 years. CRC incidence is affected by age, sex, environmental, dietary, hormonal, and lifestyle factors. Obesity is a known disease that is spreading rapidly throughout the world. A large body of literature indicates that, among many conditions, obesity is the increasing cause of CRC. Even though obesity is one of the known factors for CRC development, limited studies are available that explain the mechanistic link between obesity, sex hormones, and CRC development. Thus, this review summarizes the literature and aims to understand sex-dependent differences in CRC, especially in the context of obesity.

Keywords: adipokine; colorectal cancer; estrogen; inflammatory cytokine; obesity; sex hormone.

Figure 1

Factors influencing CRC risk. Factors influencing CRC risk are indicated by arrows where a red arrow indicates high risk while a green arrow low risk of developing CRC. (1) Elderly people are at high risk of CRC development; (2) compared to males, females have a lower risk of developing CRC due to the protective effect of estrogen. However, CRC development risk is increased in females over 65 years of age compared to males of similar age; (3) molecular changes such as CIN, MSI, and CIMP as well as families with a strong history of CRC increase the risk of developing CRC; (4) lifestyle of high consumption of alcohol, heavy smoking, and consumption of red meat and processed red meat amplifies CRC risk; (5) on the other hand, regular exercise and dietary habit of including fruits and vegetables that have high fibers have been reported to reduce CRC risk; (6) alteration of the gut microbiome can affect the CRC risk in both directions; (7) disease such as obesity has been strongly related to CRC development; moreover, obese males are at higher risk of developing CRC than obese females as females have the local estrogen production by adipose tissue.