Genetics of endometrial cancer.

[cowden syndrome]

Women who report a history of endometrial cancer in a first -degree relative are at increased risk of endometrial cancer , with a hazard ratio of 1 .5 to 2 .0 . Only a minority of patients with familial endometrial cancer have a recognized cancer syndrome . Lynch syndrome is the most common genetic syndrome associated with endometrial cancer and a marked increased risk of colon cancer . Cowden syndrome is a rare condition resulting from a mutation in the tumor suppressor gene phosphatase and tensin homolog . The risk for endometrial cancer is about five times higher in women with Cowden syndrome than in the general population . Recently , a novel germline mutation in the POLD 1 gene that encodes the catalytic subunit of DNA polymerase δ was described in several families with multiple cases of endometrial cancer . This mutation is also associated with colorectal cancer . The association between BRCA 1 mutations and endometrial cancer has been investigated in several studies ; it appears that the risk of endometrial cancer is restricted to women with a history of tamoxifen exposure . In recent years , research has focused on genetic polymorphisms that are associated with endometrial cancer risk . Although many polymorphisms have been identified , their clinical significance is unclear and they have not been adapted for clinical practice .