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 said.

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 balan

Contact: Becky Soglin
University of Iowa

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