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Prohibitin T Allele Genotype Linked to Familial Breast Cancer

Prohibitin T Allele Genotype Linked to Familial Breast Cancer

ORLANDO—Women with a specific prohibitin fragment genotype (T allele) and
a first-degree relative with breast cancer appear to be at greater risk of
developing the disease than women with the prohibitin C allele genotype,
reported Eldon R. Jupe, PhD, senior research scientist, Immunology and Cancer
Program, Oklahoma Medical Research Foundation, Oklahoma City.

"It may be possible to use this in the future to help women with
first-degree relatives with breast cancer assess their own risk of disease,"
he said at the Era of Hope Department of Defense Breast Cancer Research
Program meeting.

The research team’s early work showed that prohibitin 3´untranslated
region (3´UTR) is able to arrest cell cycle progression in normal mammary
epithelial cells and breast-cancer cell lines. They discovered a 3´UTR single
nucleotide polymorphism that defines two human prohibitin alleles—C and
T—resulting in three genotypes: C/C, C/T, and T/T.

The C allele codes for a regulatory RNA that inhibits cancer cell growth
while the T allele is inactive. Of the three genotypes, T/T occurs less
frequently, in less than 3% of the general population. The T allele includes
the C/T and T/T genotypes.

"A single C to T change in prohibitin 3´UTR is enough to inactivate the
antiproliferative activity of this transcript," Dr. Jupe said. "Our
hypothesis that originated out of this basic research was that carriers of
the prohibitin T allele have an increased susceptibility to breast cancer."

Case-Control Study

The team conducted a case-control study to test the theory. They compared
the prohibitin 3´UTR genotypes of 205 women with breast cancer with those of
1,046 cancer-free women. The women were consecutively enrolled patients
having mammography at the University of Oklahoma Institute for Breast Health.
The women self-reported any family history of breast cancer. Dr. Jupe
presented an interim analysis of the results at the meeting.


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