GENETICS IN GYNECOLOGY: CANCER SCREENING
It is now known that certain breast and ovarian cancers have a genetic predisposition. Genetic tests have been developed for the detection of some of these genes. Gynecologists play a key rolein identifying individuals with a genetic disposition for can-cer and ensuring that they receive the appropriate screen-ing tests. The most important initial step in identifying women at high risk for hereditary cancers is a thorough family history. Clues to possible hereditary cancers include a history of cancers in first-degree relatives, cancers occur-ring at young ages, cancers in multiple generations, or many different cancers in one individual. Based on these findings, further testing and genetic counseling may be indicated.
The BRCA1 and BRCA2 genes have been identified as responsible for the hereditary forms of both breast and ovarian cancers. Clinically important BRCA mutations have been found in about 2% of Ashkenazi Jewish women, and are estimated to occur in about 1 in 300 to 500 women in the general non-Jewish US population. Criteria devel-oped by the U.S. Preventative Services Task Force for BRCA testing referral are as follows:
· Two first-degree relatives with breast cancer, with at least one diagnosed at under age 50
· Three or more first-degree or second-degree relatives with breast cancer at any age
· A first-degree or second-degree relative with breast and ovarian cancer
· Two or more first-degree or second-degree relatives with ovarian cancer
· A male relative with breast cancer
Because the incidence of breast cancers linked to BRCA is higher in Ashkenazi Jewish women, the testing criteria for them are slightly different. Testing for BRCA in this population is indicated if the following are present:
· Any first-degree relative with breast or ovarian cancer
· Two second-degree relatives on the same side of the family with breast or ovarian cancer.
In addition to breast cancer, other cancers have been found to have a hereditary component. A hereditary syndrome called hereditary nonpolyposis colorectal cancer type A (HNPCC type A), or Lynch I syndrome, increases therisk for developing colon cancer. A family history of colon, endometrial, ureteral, or renal cancers should alert the clinical to screen for the HNPCC-linked genes. HNPCCtype B, or Lynch II syndrome, is an autosomal dominantinherited syndrome that increases the risk for all of the cancers in Lynch I syndrome, as well as for ovarian, gastric, and pancreatic cancers. Individuals or families who meet certain criteria, which include the presence of HNPCC in two successive generations and the diagnosis of HNPCC in at least three relatives, can undergo genetic testing to determine whether they have the defective gene.