Sexual dimorphism of colorectal cancer in humans and colorectal tumors in a murine model

Abstract Background: Sexual dimorphism (SD) is the difference in morphology and physiology between sexes of the same species; in diseases, SD can reflect the susceptibility associated with gender in humans. In colorectal cancer, men have a higher incidence than women, independently between ethnicity or geographical location, suggesting that sex steroids are involved in the development of colorectal cancer. Methods: We determined sex, as a risk factor for colorectal cancer from the GLOBOCAN database; Then, we used induction of colorectal tumors by azoxymethane and dextran sulfate of sodium treatment as the experimental strategy in males and females mice; also we gonadectomized independent males and females animals. Finally, we determined in vitro proliferation of a human cell line HCT116 exposed to estradiol, testosterone or dihytrotestosterone. Results: Sex as a risk factor for colorectal cancer showed clear and statistically significant susceptibility of men in Mexico and worldwide. In the murine model of colorectal tumors, males developed more and larger tumors than females. Further analysis showed that ovariectomized females develop more tumors in number, but all about the same size. Meanwhile gonadectomized males had fewer tumors in number and smaller in size. Surprisingly, only estradiol showed an effect in vitro on the proliferation index on human cell lines of colorectal cancer. Conclusions: Men showed enhanced susceptibility to develop colorectal cáncer tan females; in the animal model, male mice presented augmented development of colorectal tumors, which was reverted in gonadectomized male mice, female mice increased the number of tumor, the above suggests that androgens have a crucial role in explaining sexual dimorphism in the incidence of colorectal cancer. Estradiol diminished the in vitro proliferation of HCT-116 colon cancer cell line, opposite, there was no change of in vitro proliferation on cells exposed to testosterone or dihydrotestosterone, therefore, the effect in vitro could be by their interaction with other cells or systems.