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MIT: Why men are more prone to liver cancer
Date:1/15/2008

tain infectious agents.

When the male mice developed chronic hepatitis, some masculine liver genes were upregulated and others turned off. At the same time, some feminine genes were reactivated. This resulted in an unpredictable gene profile termed liver-gender disruption.

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

When the researchers mapped the sex-specific genes, they found intimate associations with inflammatory pathways. In males with chronic hepatitis, some gender-specific genes were overexpressed and others underexpressed, the liver was unable to maintain normal metabolic function and cancer emerged in a significant number of the animals.

The authors propose that adult females are less vulnerable to liver-gender disruption because there is no requirement for the active signaling needed to maintain a masculine gene profile. Because the female liver follows the default developmental pathway, a greater disturbance is required to initiate the cancer process, said Rogers.

The researchers had expected that castrating male mice at one year of age when they had chronic hepatitis, but not cancer, would have a protective effect. They also gave some mice a powerful androgen 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.

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.

This study was a collaboration between the Division of Comparative Medicine and Center for Environmental Health Sciences. It would not have been possible without the expertise and team-oriented philosophy of the wonderful scientists we have here, said Rogers.


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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

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