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Estrogen study explains why more men get stomach cancer

Kathleen Blanchard's picture
Men and stomach cancer risk

A new study shows men are at higher risk of dying from cancer than women. Following a data analysis citing higher incidence of cancer in men as the reason, researchers from MIT have discovered why men are at increased risk for developing stomach cancer.

According to background information from the research, stomach, liver and colon cancer strikes more men than women. One of the reasons, say investigators, is because estrogen protects women from some cancers.

Estrogen given to male mice dramatically lowered gastric cancer

For the study, researchers gave estrogen to male mice, finding the treatment had a significant effect for lowering the incidence of stomach cancer.

Alexander Sheh, a postdoc in MIT’s Division of Comparative Medicine (DCM) and lead author of the paper said, “If we can narrow in on which estrogen effect is causing this protection, we can come up with a better therapy.”

In the study, estrogen was most effective for preventing stomach cancer in mice infected with the bacterium Helicobacter pylori that can be found in 50 percent of individuals worldwide.

The H. pylori bacterium causes changes in the stomach from inflammation that can progress to cancer in less than a year.

The finding, published in the journal Cancer Prevention Research, notes estrogen protects women from inflammation. Because men don’t have estrogen, they are more susceptible to stomach cancer.

In the study, male mice infected with H. pylori were either untreated or given Tamoxifen, which blocks estrogen’s effect, estrogen, or a combination of both. Female mice were given no treatment or just Tamoxifen.

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The male mice, in all three treatment groups were protected from gastric cancer. The treatments weren’t started until the mice developed inflammation in the stomach, or gastritis. In the non-treated group, 40 percent developed cancer of the stomach.

A surprise findings was that the treated and non- treated female mice, leading the researchers to suspect Tamoxifen acts differently in the stomach. The drug might act the same as estrogen.

Sixty genes were over expressed in the treated mice that blocked stomach cancer from estrogen. The researchers looked closely at the protein CXCL1, involved in immunity and cell movement. CXCL1 is the equivalent of IL-8 in humans and is activated in response to H. pylori.

The finding suggests estrogen protects from gastric cancer by blocking immune activation of CXCL1, or in humans IL-8 from H pylori. The next step is to find out how it happens and what molecules stop activity of CXCL1.

Estrogen somehow protects from gastric inflammation that leads to cancer; in the presence of H.pylori. The finding helps explain why men are at higher risk for developing stomach cancer.

Understanding the protective effect of the hormone makes it possible to find new prevention. In the study, estrogen was most effective for preventing cancer of the stomach caused by the bacterium Helicobacter pylori.

Past studies have also shown women who take Tamoxifen to block estrogen activity are at increased risk for stomach cancer.

James Fox, MIT professor of biological engineering and director of Division of Comparative Medicine found female mice with ovarectomy lost protection from stomach cancer. In male mice, Fox also found estrogen protected male mice from the disease when treatment was started at birth.

Image credit: Bing