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. 1990 Jun;46(6):1041–1052.

Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors.

Y Yoshimoto 1, J V Neel 1, W J Schull 1, H Kato 1, M Soda 1, R Eto 1, K Mabuchi 1
PMCID: PMC1683841  PMID: 2160192

Abstract

The risk of cancer (incidence) prior to age 20 years has been determined for children born to atomic bomb survivors and to a suitable comparison group. Tumor ascertainment was through death certificates and the tumor registries maintained in Hiroshima and Nagasaki. The rationale for the study stemmed from the evidence that a significant proportion of such childhood tumors as retinoblastoma and Wilms tumor arise on the basis of a mutant gene inherited from one parent plus a second somatic cell mutation involving the allele of this gene. Gonadal radiation doses were calculated by the recently established DS86 system, supplemented by an ad hoc system for those children for one or both of whose parents a DS86 dose could not be computed but for whom an ad hoc dose could be developed on the basis of the available information. The total data set consisted of (1) a cohort of 31,150 live-born children one or both of whose parents received greater than 0.01 Sv of radiation at the time of the atomic bombings (average conjoint gonad exposure 0.43 Sv) and (2) two suitable comparison groups totaling 41,066 children. Altogether, 43 malignant tumors were ascertained in the children of exposed parents, and 49 malignant tumors were ascertained in the two control groups. A multiple linear regression analysis revealed no increase in malignancy in the children of exposed parents. However, examination of the data suggested that only 3.0-5.0% of the tumors of childhood that were observed in the comparison groups are associated with an inherited genetic predisposition that would be expected to exhibit an altered frequency if the parental mutation rate were increased. There is thus far no confirmation of the positive findings that Nomura found in a mouse system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BATRA B. K., SRIDHARAN B. N. A STUDY OF THE PROGENY OF MICE DESCENDED FROM X-IRRADIATED FEMALES WITH SPECIAL REFERENCE TO THE GONADS. Acta Unio Int Contra Cancrum. 1964;20:1181–1186. [PubMed] [Google Scholar]
  2. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  3. Bookstein R., Lee E. Y., To H., Young L. J., Sery T. W., Hayes R. C., Friedmann T., Lee W. H. Human retinoblastoma susceptibility gene: genomic organization and analysis of heterozygous intragenic deletion mutants. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2210–2214. doi: 10.1073/pnas.85.7.2210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bundey S., Evans K. Survivors of neuroblastoma and ganglioneuroma and their families. J Med Genet. 1982 Feb;19(1):16–21. doi: 10.1136/jmg.19.1.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  6. Dao D. D., Schroeder W. T., Chao L. Y., Kikuchi H., Strong L. C., Riccardi V. M., Pathak S., Nichols W. W., Lewis W. H., Saunders G. F. Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor. Am J Hum Genet. 1987 Aug;41(2):202–217. [PMC free article] [PubMed] [Google Scholar]
  7. Draper G. J., Heaf M. M., Kinnier Wilson L. M. Occurrence of childhood cancers among sibs and estimation of familial risks. J Med Genet. 1977 Apr;14(2):81–90. doi: 10.1136/jmg.14.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  9. Friend S. H., Horowitz J. M., Gerber M. R., Wang X. F., Bogenmann E., Li F. P., Weinberg R. A. Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9059–9063. doi: 10.1073/pnas.84.24.9059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grundy P., Koufos A., Morgan K., Li F. P., Meadows A. T., Cavenee W. K. Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11. Nature. 1988 Nov 24;336(6197):374–376. doi: 10.1038/336374a0. [DOI] [PubMed] [Google Scholar]
  11. Gunz F. W., Gunz J. P., Vincent P. C., Bergin M., Johnson F. L., Bashir H., Kirk R. L. Thirteen cases of leukemia in a family. J Natl Cancer Inst. 1978 Jun;60(6):1243–1250. doi: 10.1093/jnci/60.6.1243. [DOI] [PubMed] [Google Scholar]
  12. Hartley A. L., Birch J. M., Marsden H. B., Harris M. Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma. Br J Cancer. 1986 Nov;54(5):819–823. doi: 10.1038/bjc.1986.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huff V., Compton D. A., Chao L. Y., Strong L. C., Geiser C. F., Saunders G. F. Lack of linkage of familial Wilms' tumour to chromosomal band 11p13. Nature. 1988 Nov 24;336(6197):377–378. doi: 10.1038/336377a0. [DOI] [PubMed] [Google Scholar]
  14. KOHN H. I., EPLING M. L., GUTTMAN P. H., BAILEY D. W. EFFECT OF PATERNAL (SPERMATOGONIAL) X-RAY EXPOSURE IN THE MOUSE: LIFE SPAN, X-RAY TOLERANCE, AND TUMOR INCIDENCE OF THE PROGENY. Radiat Res. 1965 Jun;25:423–444. [PubMed] [Google Scholar]
  15. Kato H., Schull W. J., Neel J. V. A cohort-type study of survival in the children of parents exposed to atomic bombings. Am J Hum Genet. 1966 Jul;18(4):339–373. [PMC free article] [PubMed] [Google Scholar]
  16. Kitchin F. D., Ellsworth R. M. Pleiotropic effects of the gene for retinoblastoma. J Med Genet. 1974 Sep;11(3):244–246. doi: 10.1136/jmg.11.3.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Koufos A., Hansen M. F., Copeland N. G., Jenkins N. A., Lampkin B. C., Cavenee W. K. Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature. 1985 Jul 25;316(6026):330–334. doi: 10.1038/316330a0. [DOI] [PubMed] [Google Scholar]
  20. Leck I. Congenital malformations and childhood neoplasms. J Med Genet. 1977 Oct;14(5):321–326. doi: 10.1136/jmg.14.5.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee E. Y., To H., Shew J. Y., Bookstein R., Scully P., Lee W. H. Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science. 1988 Jul 8;241(4862):218–221. doi: 10.1126/science.3388033. [DOI] [PubMed] [Google Scholar]
  22. Lee W. H., Bookstein R., Hong F., Young L. J., Shew J. Y., Lee E. Y. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science. 1987 Mar 13;235(4794):1394–1399. doi: 10.1126/science.3823889. [DOI] [PubMed] [Google Scholar]
  23. Li F. P., Fraumeni J. F., Jr, Mulvihill J. J., Blattner W. A., Dreyfus M. G., Tucker M. A., Miller R. W. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988 Sep 15;48(18):5358–5362. [PubMed] [Google Scholar]
  24. 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]
  25. MACMAHON B., LEVY M. A. PRENATAL ORIGIN OF CHILDHOOD LEUKEMIA. EVIDENCE FROM TWINS. N Engl J Med. 1964 May 21;270:1082–1085. doi: 10.1056/NEJM196405212702102. [DOI] [PubMed] [Google Scholar]
  26. Matsunaga E. Genetics of Wilms' tumor. Hum Genet. 1981;57(3):231–246. doi: 10.1007/BF00278936. [DOI] [PubMed] [Google Scholar]
  27. Miller R. W. Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960-67. J Natl Cancer Inst. 1971 Jan;46(1):203–209. [PubMed] [Google Scholar]
  28. 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]
  29. Neel J. V., Kato H., Schull W. J. Mortality in the children of atomic bomb survivors and controls. Genetics. 1974 Feb;76(2):311–336. doi: 10.1093/genetics/76.2.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nomura T. Parental exposure to x rays and chemicals induces heritable tumours and anomalies in mice. Nature. 1982 Apr 8;296(5857):575–577. doi: 10.1038/296575a0. [DOI] [PubMed] [Google Scholar]
  31. Otake M., Schull W. J., Neel J. V. Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis. Radiat Res. 1990 Apr;122(1):1–11. [PubMed] [Google Scholar]
  32. Vogel F. Genetics of retinoblastoma. Hum Genet. 1979 Nov 1;52(1):1–54. doi: 10.1007/BF00284597. [DOI] [PubMed] [Google Scholar]
  33. Zuelzer W. W., Cox D. E. Genetic aspects of leukemia. Semin Hematol. 1969 Jul;6(3):228–249. [PubMed] [Google Scholar]

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