Progesterone receptor gene mutants associated with ovarian cancer

Mutations in the progesterone receptor gene (PGR) are associated with an increased risk of ovarian cancer, according to a new report.

'It appears that progesterone signaling is associated with risk of ovarian cancer, but the clinical implications of this research are not yet known,' Dr. David Altshuler from Broad Institute/MIT Center for Genome Research, Cambridge, Massachusetts told Reuters Health. 'It is important to obtain further replication, as clinical care should only be based on rock-solid and robust findings.'Dr. Altshuler and colleagues investigated the association of common sequence variations across PGR with ovarian and breast cancer risk. They report their findings in the January 5th Journal of the National Cancer Institute.Women with two copies of one PGR variant (called PROGINS, the minor allele of the rs1042838 single nucleotide polymorphism) face more than a 3-fold increased risk of ovarian cancer relative to noncarriers, the authors report.Another variant (rs608995) was also associated with an increased risk of ovarian cancer, regardless of the presence of PROGINS, the report indicates.None of the remaining single-nucleotide polymorphisms was associated with a statistically significant increased risk of ovarian cancer, the researchers note.Haplotype analysis revealed significant associations of two haplotypes (4-D and 4-E) with more than a 4-fold increased risk of ovarian cancer in women with two copies of either haplotype or one copy of each haplotype, the investigators report.These variants were associated with a nonstatistically significant reduction in the risk for breast cancer, the study shows.'Our data suggest that any influence of genetic variation in the PGR on risk of ovarian cancer is related not to the variant form of PROGINS itself but, rather, to two common haplotypes (4-D and 4-E), only one of which harbors the PROGINS allele,' the authors conclude.'We are narrowing down the region which harbors the putative risk variant,' co-researcher Dr. Celeste Leigh Pearce from University of Southern California, Keck School of Medicine, Los Angeles, told Reuters Health. 'We are sequencing these regions to identify all possible variation. We will then carry out additional genotyping on our ovarian cancer cases and controls to look for a stronger relationship to ovarian cancer risk.''Our hope is that by discovering such genetic risk factors, clinical trials can ultimately be designed to test strategies to improve outcomes based on genetic predictors, and in the long run, develop new approaches to prevention and treatment based on a better understanding of the root cause of disease,' Dr. Altshuler concluded.(Source: J Natl Cancer Inst 2005;97:51-59: Reuters Health: Will Boggs, MD: Oncolink: January 2005.)