Abstract
Age distributions of parents at birth of patients registered in the National Wilms' Tumour Study were compared to those of the general population. An increasing incidence of sporadic Wilms' tumour with increasing paternal age was found, with a relative risk of 2.1 of tumour in children of fathers over 55 compared to children of fathers younger than 20. A similar effect for maternal age was found, with a relative risk of 1.4 in children of mothers over 40 compared to children of mothers younger than 20. The maternal age effect was much weaker among patients registered later in the study; in the later, more completely ascertained cohort, paternal age appears to be the major contributor to the parental age effect. Little difference in paternal age distribution was found between patients with bilateral and unilateral tumour and between male and female patients. In contrast, patients with reported associated congenital anomalies, patients with evidence of nephrogenic rests, and patients with early or late age-of-onset of tumour had parents who were, on average, substantially older than the remainder. These findings lend support to the idea that many Wilms' tumours result from new germline mutations. Further, the histologic composition of such tumours may be sufficiently distinct as to provide a valuable diagnostic indicator of the etiology of these tumours.
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Selected References
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- Beckwith J. B., Kiviat N. B., Bonadio J. F. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor. Pediatr Pathol. 1990;10(1-2):1–36. doi: 10.3109/15513819009067094. [DOI] [PubMed] [Google Scholar]
- Breslow N., Beckwith J. B., Ciol M., Sharples K. Age distribution of Wilms' tumor: report from the National Wilms' Tumor Study. Cancer Res. 1988 Mar 15;48(6):1653–1657. [PubMed] [Google Scholar]
- Comings D. E. A general theory of carcinogenesis. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3324–3328. doi: 10.1073/pnas.70.12.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huff V., Meadows A., Riccardi V. M., Strong L. C., Saunders G. F. Parental origin of de novo constitutional deletions of chromosomal band 11p13. Am J Hum Genet. 1990 Jul;47(1):155–160. [PMC free article] [PubMed] [Google Scholar]
- Knudson A. G., Jr, Strong L. C. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. 1972 Feb;48(2):313–324. [PubMed] [Google Scholar]
- Li F. P., Gimbrere K., Gelber R. D., Sallan S. E., Flamant F., Green D. M., Heyn R. M., Meadows A. T. Outcome of pregnancy in survivors of Wilms' tumor. JAMA. 1987 Jan 9;257(2):216–219. [PubMed] [Google Scholar]
- Mannens M., Slater R. M., Heyting C., Bliek J., de Kraker J., Coad N., de Pagter-Holthuizen P., Pearson P. L. Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum Genet. 1988 Dec;81(1):41–48. doi: 10.1007/BF00283727. [DOI] [PubMed] [Google Scholar]
- Mulvihill J. J., Myers M. H., Connelly R. R., Byrne J., Austin D. F., Bragg K., Cook J. W., Hassinger D. D., Holmes F. F., Holmes G. F. Cancer in offspring of long-term survivors of childhood and adolescent cancer. Lancet. 1987 Oct 10;2(8563):813–817. doi: 10.1016/s0140-6736(87)91012-9. [DOI] [PubMed] [Google Scholar]
- Pal N., Wadey R. B., Buckle B., Yeomans E., Pritchard J., Cowell J. K. Preferential loss of maternal alleles in sporadic Wilms' tumour. Oncogene. 1990 Nov;5(11):1665–1668. [PubMed] [Google Scholar]
- Pelletier J., Bruening W., Li F. P., Haber D. A., Glaser T., Housman D. E. WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature. 1991 Oct 3;353(6343):431–434. doi: 10.1038/353431a0. [DOI] [PubMed] [Google Scholar]
- Pellié C., Briard M. L., Feingold J., Frézal J. Parental age in retinoblastoma. Humangenetik. 1973;20(1):59–62. doi: 10.1007/BF00280877. [DOI] [PubMed] [Google Scholar]
- Pritchard-Jones K., Fleming S. Cell types expressing the Wilms' tumour gene (WT1) in Wilms' tumours: implications for tumour histogenesis. Oncogene. 1991 Dec;6(12):2211–2220. [PubMed] [Google Scholar]
- Riccardi V. M., Dobson C. E., 2nd, Chakraborty R., Bontke C. The pathophysiology of neurofibromatosis: IX. Paternal age as a factor in the origin of new mutations. Am J Med Genet. 1984 May;18(1):169–176. doi: 10.1002/ajmg.1320180121. [DOI] [PubMed] [Google Scholar]
- Risch N., Reich E. W., Wishnick M. M., McCarthy J. G. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987 Aug;41(2):218–248. [PMC free article] [PubMed] [Google Scholar]
- Vogel F., Rathenberg R. Spontaneous mutation in man. Adv Hum Genet. 1975;5:223–318. doi: 10.1007/978-1-4615-9068-2_4. [DOI] [PubMed] [Google Scholar]
