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Why Are Men More Prone to Developing Liver Cancer?

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Massachusetts Institute of Technology (MIT) researchers believe they’ve found a gender effect that may explain why men are more prone to liver cancer than women. It all boils down to the way males and females respond to chronic liver disease at the genetic level.

“It's an epidemic waiting to happen,” said Arlin Rogers, an experimental pathologist and principal research scientist in MIT's Division of Comparative Medicine. Rogers undertook the first genome-wide study that “helps explain why there is such a gender effect in a cancer of a non-reproductive organ, where you wouldn't expect to see one.”

Liver cancer is the fifth most common cancer in the world and the third biggest killer. In the U.S., men currently develop liver cancer at twice the rate of women, but those rates are rising rapidly. In other countries, especially in Asia, the rate for men can be eight to 10 times that for women.

Researchers say the surge is due, in part, to high hepatitis C infection rates during the 1970s from blood transfusions and IV drug abuse. Obesity and type two diabetes are additional risk factors of current concern.

Male and female livers are inherently different, particularly during puberty when male livers are exposed to periodic bursts of growth hormone and express different genes than female livers.

These differences explain why men and women can have different reactions to certain antibiotics and other medications, according to the research.

For the study, published in journal Cancer Research, the MIT team analyzed mice, because like humans, they also have higher liver cancer rates among males. In both species, healthy males and females respond to acute toxins and other stresses, but the male liver is less well equipped to cope with the chronic inflammation induced by certain infectious agents.

To study this effect, the mice were infected with Helicobacter hepaticus, bacterium found in the gastrointestinal tract or in liver tissue of humans. In mice, it produces the same hepatitis symptoms characteristic of human hepatitis B and C.

When the male mice developed chronic hepatitis, the researchers observed something unexpected. Some masculine liver genes increased while others turned off allowing cancer to emerge in a significant number of animals. At the same time, some feminine genes were reactivated rendering females less susceptible to cancer.

“There's no rhyme or reason to it. There's just a complete scrambling of masculine and feminine genes,” said Rogers.

The researchers had a hunch that a protective effect would emerge if male mice were castrated at one year of age when they had chronic hepatitis, but not cancer. Researchers also gave some mice a powerful male hormone to see if that would promote tumors. Neither treatment had any effect, demonstrating that male sex hormones such as testosterone do not directly promote liver cancer in adults.
However, these results could be relevant to cancers of other organs, such as the stomach and colon, which also are associated with chronic inflammation and are more common in men.

The study was a collaboration between the Division of Comparative Medicine and Center for Environmental Health Sciences and funded by the National Institutes of Health.

Lynette Summerill, is an award-winning journalist who lives in Scottsdale, Arizona. In addition to writing about cancer-related issues, she writes a blog, Nonsmoking Nation, which follows global tobacco news and events

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