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. 1993 Aug;68(2):357–363. doi: 10.1038/bjc.1993.340

Congenital abnormalities in children with cancer and their relatives: results from a case-control study (IRESCC).

J R Mann 1, H E Dodd 1, G J Draper 1, J A Waterhouse 1, J M Birch 1, R A Cartwright 1, A L Hartley 1, P A McKinney 1, C A Stiller 1
PMCID: PMC1968541  PMID: 8347491

Abstract

Several studies have revealed an excess of malformations in children with certain malignancies. A few environmental causes have been identified which may damage the foetus and lead to malformation and cancer. However, most of the numerous recognised cancer/malformation syndromes are genetically determined. This report describes a case-control study of 555 newly diagnosed children with cancer and 1,110 matched controls, chosen from general practitioner lists (GP controls) and hospital admissions (H controls). Their parents were interviewed on topics of possible aetiological significance and medical records were checked to confirm reports at interview. The numbers of congenital malformations in the index and GP control children, and the relatives of the index children, the GP and H controls are described. There were more children with malformations among the cases (60/555) than among the GP controls (27/555), P < 0.001. The abnormalities in the cases included eight with specific chromosomal/genetic conditions (e.g. Down's syndrome, XY gonadal dysgenesis, Von Recklinghausen's neurofibromatosis, Goldenhar's syndrome) whereas only one GP control child had a chromosomal defect (P < 0.05). Five case children but no GP controls had neural tube defects; this is not statistically significant. No excess of malformations was found in the siblings of cases compared with GP and H control siblings. Case mothers had a small excess of malformations (22/555) compared with GP controls (8/555), P < 0.05. Among more distant relatives the results were difficult to interpret because of the relatively small numbers in the diagnostic subgroups and because of apparent under reporting in grandparents, but no striking differences were seen between case and control relatives. The excess of malformations found in children with cancer, compared with controls, without a similar excess of malformations in their close relatives may indicate that in some (perhaps very roughly one in 20) cases antenatal events may lead both to the malformation and the malignancy.

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Selected References

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  1. Bibbo M., Gill W. B., Azizi F., Blough R., Fang V. S., Rosenfield R. L., Schumacher G. F., Sleeper K., Sonek M. G., Wied G. L. Follow-up study of male and female offspring of DES-exposed mothers. Obstet Gynecol. 1977 Jan;49(1):1–8. [PubMed] [Google Scholar]
  2. Birch J. M. Anencephaly in stillborn sibs of children with germ cell tumours. Lancet. 1980 Jun 7;1(8180):1257–1257. doi: 10.1016/s0140-6736(80)91724-9. [DOI] [PubMed] [Google Scholar]
  3. Birch J. M., Hartley A. L., Teare M. D., Blair V., McKinney P. A., Mann J. R., Stiller C. A., Draper G. J., Johnston H. E., Cartwright R. A. The inter-regional epidemiological study of childhood cancer (IRESCC): case-control study of children with central nervous system tumours. Br J Neurosurg. 1990;4(1):17–25. doi: 10.3109/02688699009000677. [DOI] [PubMed] [Google Scholar]
  4. Birch J. M., Mann J. R., Cartwright R. A., Draper G. J., Waterhouse J. A., Hartley A. L., Johnston H. E., McKinney P. A., Stiller C. A., Hopton P. A. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCO). Study design, control selection and data collection. Br J Cancer. 1985 Dec;52(6):915–922. doi: 10.1038/bjc.1985.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birch J. M., Marsden H. B., Swindell R. Pre-natal factors in the origin of germ cell tumours of childhood. Carcinogenesis. 1982;3(1):75–80. doi: 10.1093/carcin/3.1.75. [DOI] [PubMed] [Google Scholar]
  6. Brown L. M., Pottern L. M., Hoover R. N. Prenatal and perinatal risk factors for testicular cancer. Cancer Res. 1986 Sep;46(9):4812–4816. [PubMed] [Google Scholar]
  7. 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]
  8. Ehrenbard L. T., Chaganti R. S. Cancer in the fetal hydantoin syndrome. Lancet. 1981 Jul 11;2(8237):97–97. doi: 10.1016/s0140-6736(81)90452-9. [DOI] [PubMed] [Google Scholar]
  9. Fraumeni J. F., Jr, Li F. P., Dalager N. Teratomas in children: epidemiologic features. J Natl Cancer Inst. 1973 Nov;51(5):1425–1430. doi: 10.1093/jnci/51.5.1425. [DOI] [PubMed] [Google Scholar]
  10. GILES D., HEWITT D., STEWART A., WEBB J. Malignant disease in childhood and diagnostic irradiation in utero. Lancet. 1956 Sep 1;271(6940):447–447. doi: 10.1016/s0140-6736(56)91923-7. [DOI] [PubMed] [Google Scholar]
  11. Green A. R. Recessive mechanisms of malignancy. Br J Cancer. 1988 Aug;58(2):115–121. doi: 10.1038/bjc.1988.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herbst A. L., Ulfelder H., Poskanzer D. C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878–881. doi: 10.1056/NEJM197104222841604. [DOI] [PubMed] [Google Scholar]
  13. Hethcote H. W., Knudson A. G., Jr Model for the incidence of embryonal cancers: application to retinoblastoma. Proc Natl Acad Sci U S A. 1978 May;75(5):2453–2457. doi: 10.1073/pnas.75.5.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hornstein L., Crowe C., Gruppo R. Adrenal carcinoma in child with history of fetal alcohol syndrome. Lancet. 1977 Dec 17;2(8051):1292–1293. doi: 10.1016/s0140-6736(77)92706-4. [DOI] [PubMed] [Google Scholar]
  15. Johnston H. E., Mann J. R., Williams J., Waterhouse J. A., Birch J. M., Cartwright R. A., Draper G. J., Hartley A. L., McKinney P. A., Hopton P. A. The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumours. Carcinogenesis. 1986 May;7(5):717–722. doi: 10.1093/carcin/7.5.717. [DOI] [PubMed] [Google Scholar]
  16. Khan A., Bader J. L., Hoy G. R., Sinks L. F. Hepatoblastoma in child with fetal alcohol syndrome. Lancet. 1979 Jun 30;1(8131):1403–1404. doi: 10.1016/s0140-6736(79)92035-x. [DOI] [PubMed] [Google Scholar]
  17. Knudson A. G., Jr Genetics of human cancer. Annu Rev Genet. 1986;20:231–251. doi: 10.1146/annurev.ge.20.120186.001311. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Knudson A. G., Jr Retinoblastoma: a prototypic hereditary neoplasm. Semin Oncol. 1978 Mar;5(1):57–60. [PubMed] [Google Scholar]
  20. Leck I., Record R. G., McKeown T., Edwards J. H. The incidence of malformations in Birmingham, England, 1950-1959. Teratology. 1968 Aug;1(3):263–280. doi: 10.1002/tera.1420010305. [DOI] [PubMed] [Google Scholar]
  21. MILLER R. W., FRAUMENI J. F., Jr, MANNING M. D. ASSOCIATION OF WILMS'S TUMOR WITH ANIRIDIA, HEMIHYPERTROPHY AND OTHER CONGENITAL MALFORMATIONS. N Engl J Med. 1964 Apr 30;270:922–927. doi: 10.1056/NEJM196404302701802. [DOI] [PubMed] [Google Scholar]
  22. Mann J. R., Corkery J. J., Fisher H. J., Cameron A. H., Mayerová A., Wolf U., Kennaugh A. A., Woolley V. The X linked recessive form of XY gonadal dysgenesis with a high incidence of gonadal germ cell tumours: clinical and genetic studies. J Med Genet. 1983 Aug;20(4):264–270. doi: 10.1136/jmg.20.4.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mann J. R., Kasthuri N., Raafat F., Pincott J. R., Parkes S. E., Muir K. R., Ingram L. C., Cameron A. H. Malignant hepatic tumours in children: incidence, clinical features and aetiology. Paediatr Perinat Epidemiol. 1990 Jul;4(3):276–289. doi: 10.1111/j.1365-3016.1990.tb00651.x. [DOI] [PubMed] [Google Scholar]
  24. Mole R. H. Radiation effects on pre-natal development and their radiological significance. Br J Radiol. 1979 Feb;52(614):89–101. doi: 10.1259/0007-1285-52-614-89. [DOI] [PubMed] [Google Scholar]
  25. Riccardi V. M., Sujansky E., Smith A. C., Francke U. Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. Pediatrics. 1978 Apr;61(4):604–610. [PubMed] [Google Scholar]
  26. Ruymann F. B., Maddux H. R., Ragab A., Soule E. H., Palmer N., Beltangady M., Gehan E. A., Newton W. A., Jr Congenital anomalies associated with rhabdomyosarcoma: an autopsy study of 115 cases. A report from the Intergroup Rhabdomyosarcoma Study Committee (representing the Children's Cancer Study Group, the Pediatric Oncology Group, the United Kingdom Children's Cancer Study Group, and the Pediatric Intergroup Statistical Center). Med Pediatr Oncol. 1988;16(1):33–39. doi: 10.1002/mpo.2950160109. [DOI] [PubMed] [Google Scholar]
  27. Yunis J. J. The chromosomal basis of human neoplasia. Science. 1983 Jul 15;221(4607):227–236. doi: 10.1126/science.6336310. [DOI] [PubMed] [Google Scholar]

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