CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-9917
Release: March 2, 1999
UI researchers find possible genetic link between the X chromosome
and ovarian cancer
IOWA CITY, Iowa -- An imbalance in how genes are expressed on a female's
two X chromosomes may lead to the development of ovarian cancer in some
women, University of Iowa Cancer Center researchers report in a study published
in the Feb. 17 issue of the Journal of the National Cancer Institute.
The study's principal investigator, Richard E. Buller, M.D., Ph.D.,
UI professor of obstetrics and gynecology, and pharmacology, said the research
suggests that a gene on the X chromosome that is involved with invasive
ovarian cancer may also influence the effects of BRCA1, a separate gene
known to cause hereditary breast and ovarian cancer.
The study examined 213 women with invasive ovarian cancer, 44 women
with borderline ovarian cancer and 50 women without any personal or family
history of cancer. Eleven of the women who inherited BRCA1 gene mutations
were among those with invasive ovarian cancer. Of those 11 women, nine
had nonrandom X-chromosome inactivation, a genetic condition in which one
set of chromosomes, either maternal or paternal, is more active in all
cells of the body.
"This suggests that there may be a factor on the X chromosome that
interacts with the BRCA1 gene product or influences its expression. This
phenomenon could explain why women in the same family carrying the same
BRCA1 mutation develop cancer at significantly different ages," Buller
Buller explained that the cells of female embryos each contain two X
chromosomes, one from each parent. In the early stages of development,
one of the X chromosomes is "turned off" in each cell to avoid
biological problems that would otherwise develop if both chromosomes remained
active. Usually, the process of one chromosome becoming inactive is random
and, as a result, a female ends up genetically as a "mosaic"
with nearly the same number of cells containing an active paternal X chromosome
as cells containing an active maternal X chromosome.
But as the study showed, this genetic balance is usually not the case
for women with ovarian cancer and especially not for those who developed
ovarian cancer due to inheritance of a mutant BRCA1 gene.
"The uneven distribution violates a basic biological principle,"
Buller said his team found that in women with invasive ovarian cancer,
more than 50 percent had either a paternal or maternal chromosome active
in most, rather than in just half, of their cells. When a mutant BRCA1
gene was also present, 90 percent of the women had this nonrandom X-chromosome
inactivation. By comparison, the team found such chromosomal imbalance
in only 28 percent of the women with borderline ovarian cancer and 33 percent
of healthy women.
The next step for the UI researchers is to determine the exact location
of the gene on the X chromosome that may be interacting the BRCA1, Buller
"The research will help us learn more about risk factors for ovarian
cancer and could lead to new prevention strategies that might reduce a
woman's chance of getting breast or ovarian cancer," he said.