Genetics of Wilms' tumor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1981-05

AUTHORS

E. Matsunaga

ABSTRACT

The analyses of published data for Wilms' tumor show the following results:The mode of inheritance of familial cases, which constitute less than 1% of all Wilms' tumors, is autosomal dominant with variable penetrance and expressivity. The familial pattern reveals no evidence that this tumor is associated with a vertically transmitting tumor virus.There is a significant correlation between the first-degree relatives affected with Wilms' tumor in regard to expressivity as measured by the proportion of bilaterally affected or by the age of the patients at diagnosis. In particular, expressivity in the children affected varies consistently with expressivity in the carrier parents, indicating that inherited host resistance plays an important role in the manifestation of the major gene. The average risk of developing Wilms' tumor for offspring of unaffected carriers, who may be regarded as inherently resistant to tumor formation, is estimated at about 0.30. Although the data are limited, the risk for offspring of survivors of hereditary unilateral or bilateral cases may be as high as 0.40 or more. The data from seven pairs of monozygotic twins, including the discordant one associated with del(11 p) and aniridia, are consistent with the host resistance model.In sporadic cases, the proportion of bilateral involvement is about 3%, in contrast with 20% in the familial cases. For bilateral cases, however, the distribution of ages of the patients at diagnosis is virtually the same whether sporadic or familial, and in two-thirds of the cases the disease is already bilateral when the first tumor is noted. These findings suggest that bilateral cases are probably always hereditary. Ages of the patients at diagnosis of sporadic unilateral cases tend to be much higher than in the patients with familial unilateral cases, indicating that most sporadic unilateral cases are nonhereditary. The overall risk for survivors of sporadic unilateral Wilms' tumor to transmit the disease to children may be as low 2∼4%.Thus, a number of parallels are found between Wilms' tumor and retinoblastoma. The rate of germinal mutation per locus per generation is estimated at 3∼8×10-6 for Wilms' tumor, which does not seem to differ from 8∼14×10-6 for retinoblastoma. However, the incidence of nonhereditary Wilms' tumor per newborn is 7∼11×10-5, which is about twice that (3∼5×10-5) of nonhereditary retinoblastoma. This difference is possibly due to the greater number of cell divisions, resulting in an increased frequency of somatic mutations, of the embryonic cells involved in morphogenesis of the kidney than in the case of retinal development.With increasing success in therapeutic management, it is anticipated that more and more cases of Wilms' tumor inherited from the survivors are emerging. However, even if complete cure of the disease and full recovery of fertility could be achieved for all the patients, about 10 generations may be required to double the present incidence of Wilms' tumor in the population, provided that other conditions remained the same.Some guidelines for genetic counseling in families affected by Wilms' tumor are given. More... »

PAGES

231-246

References to SciGraph publications

  • 1978-04. Complex patterns of inheritance in human disease in NATURE
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 1979-11. Genetics of retinoblastoma in HUMAN GENETICS
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    http://scigraph.springernature.com/pub.10.1007/bf00278936

    DOI

    http://dx.doi.org/10.1007/bf00278936

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017313002

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/6265341


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