The genetics of ovarian cancer: an assessment of current screening protocols and recommendations for counseling families at risk.

Although the need for effective ovarian cancer screening is apparent, a highly sensitive and specific screening methodology has yet to be elucidated. 42-44 Given that there are more than 43 million women in the United States older than 45 years of age and that the average cost of a pelvic sonogram is $ 275 (and $ 45 for CA125 screening), the screening of this population is estimated to increase health care costs by $ 14 billion per year. 45 The additional cost of BRCA1 screening varies according to the level of diagnostic effort required to establish BRCA1 gene mutations in a particular family and ranges from $ 295 to $ 1,200 per sample. Assuming an average cost of $ 600 per sample, initial screening of these same women would likely increased costs in excess of $ 25 billion. Current knowledge and technology in ovarian cancer screening has not yet proved beneficial for the general population or for women with fewer than two affected family members. For women with two or more affected family members, there is a 3% chance of that patient being a proband in a hereditary cancer syndrome family. 11,46 In this group, who may be at increased risk for developing a malignancy, heightened surveillance is warranted, although there are still no data to confirm that screening even these high-risk women will reduce mortality. Nevertheless, annual bimanual examination, serum CA125, and transvaginal sonography are recommended among this particular subgroup of women at risk, and are likely to be recommended for young, asymptomatic, at-risk women who screen positive for the 185delAG BRCA1 deletion commonly found in persons of Ashkenazi Jewish ancestry. It is only through prospective, randomized trials that reliable data regarding the risk/benefit ratio of ovarian cancer screening among various populations at risk will be determined. The results of the prospective/randomized PLCO trial and the mature data from ongoing prospective, nonrandomized screening trials for women with a family history of cancer may provide this information and are eagerly awaited.

Cystic fibrosis in Israel: clinical and genetic aspects.

A total of 140 cases of cystic fibrosis in 110 families was identified in Israel during the years 1946--75, and there was reason to suspect inadequate ascertainment. Cystic fibrosis is frequent among the Ashkenazic and Arab populations with an incidence approximating that for Caucasians of European ancestry (1:1,800 to 1:4,000 live births). It is about half as frequent in the Sephardim, rare in the Iraqi or Yemenite Jews and perhaps absent in Iranian Jews. The clinical picture of cystic fibrosis in Israel in all the ethnic groups was found to be the same as elsewhere in the world. In-depth.interviews of 50 families were conducted to assess their understanding of the genetics of the disease and their attitude toward family planning.