Genes Key To High Liver Cancer Rates In Men

[Guest guest]

Genes Key To High Liver Cancer Rates In Men

ScienceDaily (Jan. 17, 2008) — A fundamental difference in the way males and

females respond to chronic liver disease at the genetic level helps explain why

men are more prone to liver cancer, according to MIT researchers.

“This is the first genome-wide study that helps explain why there is such a

gender effect in a cancer of a nonreproductive organ, where you wouldn't expect

to see one,” said Arlin , an MIT experimental pathologist and lead author

of a paper that appeared recently in the journal Cancer Research.

Men develop liver cancer at twice the rate of women in the United States. In

other countries, especially in Asia, the rate for men can be eight or 10 times

that for women.

Liver cancer is the fifth most common cancer in the world and the third-biggest

killer. Rates in the United States are lower than those in other countries but

are rising rapidly, in part due to high hepatitis C infection rates during the

1970s from blood transfusions and IV drug abuse. Obesity and type 2 diabetes are

additional risk factors of current concern.

“It's an epidemic waiting to happen,” said , a principal research

scientist in MIT's Division of Comparative Medicine.

Male and female livers are inherently different, with most of the differences

arising during puberty when male livers are exposed to periodic bursts of growth

hormone. This prompts male livers to express different genes than female livers,

which explains why men and women can have different reactions to certain

antibiotics and other medications.

The MIT team studied mice, which also have higher liver cancer rates among

males. The mice were infected with Helicobacter hepaticus, which produces the

same hepatitis symptoms characteristic of human hepatitis B and C.

In humans and mice, healthy males and females both can 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.

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 .

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 .

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 .

Authors of the paper are Theve, postdoctoral fellow in the Division of

Comparative Medicine (DCM); Yan Feng, research scientist in DCM; Fry,

assistant scientific director for the Center for Environmental Health Sciences

(CEHS); Koli Taghizadeh, research scientist in CEHS; Clapp, research

technician in DCM; Chakib Boussahmain, technical assistant in DCM; Kathleen

Cormier, supervisor of histology in DCM; and senior author Fox, director

of DCM and a professor in MIT's Department of Biological Engineering.

The research was funded by the National Institutes of Health.

Adapted from materials provided by Massachusetts Institute of Technology.

http://www.sciencedaily.com/releases/2008/01/080115151302.htm

_________________________________________________________________

Connect and share in new ways with Windows Live.

http://www.windowslive.com/share.html?ocid=TXT_TAGHM_Wave2_sharelife_012008

[Guest guest]

Genes Key To High Liver Cancer Rates In Men

ScienceDaily (Jan. 17, 2008) — A fundamental difference in the way males and

females respond to chronic liver disease at the genetic level helps explain why

men are more prone to liver cancer, according to MIT researchers.

“This is the first genome-wide study that helps explain why there is such a

gender effect in a cancer of a nonreproductive organ, where you wouldn't expect

to see one,” said Arlin , an MIT experimental pathologist and lead author

of a paper that appeared recently in the journal Cancer Research.

Men develop liver cancer at twice the rate of women in the United States. In

other countries, especially in Asia, the rate for men can be eight or 10 times

that for women.

Liver cancer is the fifth most common cancer in the world and the third-biggest

killer. Rates in the United States are lower than those in other countries but

are rising rapidly, in part due to high hepatitis C infection rates during the

1970s from blood transfusions and IV drug abuse. Obesity and type 2 diabetes are

additional risk factors of current concern.

“It's an epidemic waiting to happen,” said , a principal research

scientist in MIT's Division of Comparative Medicine.

Male and female livers are inherently different, with most of the differences

arising during puberty when male livers are exposed to periodic bursts of growth

hormone. This prompts male livers to express different genes than female livers,

which explains why men and women can have different reactions to certain

antibiotics and other medications.

The MIT team studied mice, which also have higher liver cancer rates among

males. The mice were infected with Helicobacter hepaticus, which produces the

same hepatitis symptoms characteristic of human hepatitis B and C.

In humans and mice, healthy males and females both can 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.

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 .

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 .

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 .

Authors of the paper are Theve, postdoctoral fellow in the Division of

Comparative Medicine (DCM); Yan Feng, research scientist in DCM; Fry,

assistant scientific director for the Center for Environmental Health Sciences

(CEHS); Koli Taghizadeh, research scientist in CEHS; Clapp, research

technician in DCM; Chakib Boussahmain, technical assistant in DCM; Kathleen

Cormier, supervisor of histology in DCM; and senior author Fox, director

of DCM and a professor in MIT's Department of Biological Engineering.

The research was funded by the National Institutes of Health.

Adapted from materials provided by Massachusetts Institute of Technology.

http://www.sciencedaily.com/releases/2008/01/080115151302.htm

_________________________________________________________________

Connect and share in new ways with Windows Live.

http://www.windowslive.com/share.html?ocid=TXT_TAGHM_Wave2_sharelife_012008