C I Amos1, J P Struewing. 1. Genetic Studies Section, National Institute of Arthritis, Musculoskeletal and and Skin Diseases, Bethesda, MD 20892.
Abstract
BACKGROUND: Aside from age, family history is the strongest predictor of ovarian cancer risk. Genetic components of risk for ovarian cancer have been evaluated by a number of designs, including case-control studies of family history and other risk factors, segregation and genetic linkage studies, and studies of biomarkers and tumor-specific cytogenetic abnormalities. METHODS: Data were extracted from all available case-control studies that included family history. Cytogenetic, biomarker, segregation, analytic, and genetic linkage studies were reviewed. RESULTS: Family history of ovarian cancer confers a 3.6-fold increased risk for this disease. Segregation studies of breast and ovarian cancer in five large families were consistent with dominant inheritance. Low levels of alpha-L-fucosidase confer mildly increased risk for ovarian cancer. Low galactose-1-phosphate uridyl transferase and type A blood group may increase risk for ovarian cancer. Cytogenetic and oncogene studies have identified regions that may be important in tumorigenesis and metastasis, but discriminating between early and late changes is difficult from these studies. Presence of a genetic susceptibility locus for breast and ovarian cancer has been confirmed on chromosome 17q21. CONCLUSIONS: Family history is an important predictor of ovarian cancer risk. In rare families, a specific dominantly acting gene can be identified, but in the vast majority of familial ovarian cancers the underlying mechanism remains unclear. Specific studies are needed for women with a family history of ovarian cancer because evidence suggests modification of the effects of oral contraceptive use and reproductive patterns in this population of women.
BACKGROUND: Aside from age, family history is the strongest predictor of ovarian cancer risk. Genetic components of risk for ovarian cancer have been evaluated by a number of designs, including case-control studies of family history and other risk factors, segregation and genetic linkage studies, and studies of biomarkers and tumor-specific cytogenetic abnormalities. METHODS: Data were extracted from all available case-control studies that included family history. Cytogenetic, biomarker, segregation, analytic, and genetic linkage studies were reviewed. RESULTS: Family history of ovarian cancer confers a 3.6-fold increased risk for this disease. Segregation studies of breast and ovarian cancer in five large families were consistent with dominant inheritance. Low levels of alpha-L-fucosidase confer mildly increased risk for ovarian cancer. Low galactose-1-phosphate uridyl transferase and type A blood group may increase risk for ovarian cancer. Cytogenetic and oncogene studies have identified regions that may be important in tumorigenesis and metastasis, but discriminating between early and late changes is difficult from these studies. Presence of a genetic susceptibility locus for breast and ovarian cancer has been confirmed on chromosome 17q21. CONCLUSIONS: Family history is an important predictor of ovarian cancer risk. In rare families, a specific dominantly acting gene can be identified, but in the vast majority of familial ovarian cancers the underlying mechanism remains unclear. Specific studies are needed for women with a family history of ovarian cancer because evidence suggests modification of the effects of oral contraceptive use and reproductive patterns in this population of women.
Authors: R Moslehi; W Chu; B Karlan; D Fishman; H Risch; A Fields; D Smotkin; Y Ben-David; J Rosenblatt; D Russo; P Schwartz; N Tung; E Warner; B Rosen; J Friedman; J S Brunet; S A Narod Journal: Am J Hum Genet Date: 2000-03-16 Impact factor: 11.025