This paper presents the analysis of familial cancer data collected in a hospital-based study of 159 childhood soft-tissue-sarcoma patients. Two different statistical models detected excess aggregation of cancer, which could be explained by a rare dominant gene. For each kindred, we estimated the probability of the observed cancer distribution under the dominant-gene model and identified 12 families that are the most likely to be segregating the gene. Two of those families have confirmed germ-line mutations in the p53 tumor-suppressor gene. The relative risk of affection for children who are gene carriers was estimated to be 100 times the background rate. Females were found to have a slightly higher age-specific penetrance, but maternal and paternal lineages made equal contributions to the evidence in favor of the dominant gene. The proband's histology, ethnicity, and age at diagnosis were evaluated to determine whether any of these altered the probability of affection in family members. Only embryonal rhabdomyosarcoma was found to be a significant covariate under the dominant-gene model. While molecular genetic studies of familial cancer will eventually provide answers to the questions of genetic heterogeneity, age- and site-specific penetrance, mutation rates, and gene frequency, information from statistical models is useful for setting priorities and defining hypotheses.
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Cites: Cancer Res. 1991 Dec 1;51(23 Pt 1):6385-71933902
Cites: J Natl Cancer Inst. 1969 Dec;43(6):1365-735396222
Cites: Cancer. 1990 Nov 15;66(10):2239-482224780
Cites: Cancer Res. 1988 Sep 15;48(18):5358-623409256
Cites: Proc Natl Acad Sci U S A. 1989 May;86(9):3247-512566168
Cites: Proc Natl Acad Sci U S A. 1989 Oct;86(19):7480-42798419
Cites: Br J Cancer. 1988 Jan;57(1):127-93348946
Cites: Biometrics. 1986 Sep;42(3):611-253567294
Cites: Br J Radiol. 1987 Jan;60(709):89-903815001
Cites: Br J Cancer. 1990 Feb;61(2):3412310687
Cites: Oncology. 1990;47(1):75-92300390
Cites: J Med Genet. 1982 Oct;19(5):362-56958872
Cites: Hum Hered. 1981;31(5):312-217333620
Cites: Hum Genet. 1979 Nov 1;52(1):1-54393614
Cites: Cancer. 1971 Aug;28(2):519-285284468
Cites: Science. 1990 Nov 30;250(4985):1233-81978757