The female sex hormone, estrogen, reduces the risk of stomach cancer, confirms the latest research published in the journal Cancer Prevention Research. According to the authors of the study, it allows not only to better understand why women are less exposed to this malignant tumor, but it can also contribute to the development of new methods of its treatment.
Of course, oncologists are unlikely to use estrogen in men with stomach cancer, but the latest research could help develop new drugs that mimic the hormone’s inhibiting effect on certain types of cancer. If we are able to clarify how estrogen exerts its protective effect, it will be possible to develop a new treatment method, comments lead author Dr. Alexander Sheh of the Massachusetts Institute of Technology in Cambridge, Massachusetts.
The researchers reminded that some malignant neoplasms, including colon, stomach and liver cancer, are much more common in men than in women. Some researchers have previously suggested that this may be due to a different lifestyle, such as a different diet or differences in smoking, but increasing scientific evidence indicates that it is the result of fundamental biological differences between the sexes.
This is also confirmed by the latest research that was conducted on male mice. The administration of estrogen to them clearly protected the animals against the development of gastric cancer, especially related to chronic Helicobacter pylori infection.
This bacterium is infected over 50 percent. world population, although most people have no symptoms because the infection is kept under control by the immune system. Over time, however, chronic inflammation in the stomach and ulcer disease may develop. Chronic gastritis associated with H. pylori infection also increases the risk of gastric cancer.
Previous research has shown that estrogen may protect women to some extent from H. pylori-induced inflammation and thus reduce the risk of stomach cancer. For example, ladies who reach the menopause later and who are more fertile (that is, produce sex hormones for longer or have no hormonal abnormalities) are less likely to develop this cancer.
In addition, female mice that do not produce estrogen due to ovariectomy increase the risk of gastric cancer, and administering estrogen to males shortly after birth prevents the development of chronic inflammation and precancerous changes in the stomach.
The latest experiments were carried out in genetically altered mice that produce very large amounts of gastrin, a hormone that stimulates the production of stomach acid. These rodents typically develop gastric cancer within 20 months of life. Infection with H. pylori reduces this time to about seven months. And just like humans, males get sick much more often than females.
Sixteen weeks after the males were infected with H. pylori, when they developed an inflammation in the stomach, the researchers injected the animals with estrogen-releasing preparations, either a drug called tamoxifen, or both, for 16 weeks. The fourth group received placebo implants. Females received either tamoxifen or a placebo.
Tamoxifen is used to treat hormone-dependent breast cancer. By acting on the same receptor as estrogen, it blocks its stimulating effect on cancer cells.
Therefore, the researchers expected that tamoxifen would detract from the protective effects of estrogen in the mice of both sexes tested. To their surprise, males given estrogen, tamoxifen, or both were equally protected against stomach cancer. None of them fell ill with this cancer, while in the untreated group – as much as 40 percent.
Tamoxifen did not affect the lesions in the stomachs of females, regardless of whether they were infected with H. pylori or not.
This suggests that in the stomach, tamoxifen may mimic rather than counteract the effects of estrogen, the authors believe.
Further tests showed that in males treated with estrogen or tamoxifen, the activity of various genes changed, some of which are involved in tumor development, cell migration and metastasis. These animals produced less of the protein known as CXCL1, of which the human equivalent is called interleukin 8 (IL-8). It is a signal that encourages immune cells called neutrophils to migrate.
In chronic H. pylori infection, when CXCL1 (IL-8) production is elevated, neutrophils enter the gastric mucosa where they contribute to inflammation and later to inflammation and cancer. Blocking, among others this process by estrogen or tamoxifen could be the mechanism explaining why both compounds protect against stomach cancer.
Researchers hope that in the future they will be able to develop drugs that inhibit the activity of the CXCL1 protein, which will help treat patients with this cancer (PAP).