Epidemiology

Case–control study of paternal occupational exposures and childhood bone tumours and soft-tissue sarcomas in Great Britain, 1962–2010

Subjects

Abstract

Background

This nationwide study investigated associations between paternal occupational exposure and childhood bone tumours and soft- tissue sarcomas.

Methods

The UK National Registry of Childhood Tumours provided cases of childhood sarcomas born and diagnosed in Great Britain, 1962–2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers’ occupations were assigned to one or more of 33 exposure groups and coded for occupational social class.

Results

We analysed 5,369 childhood sarcoma cases and 5380 controls. Total bone tumours, total soft-tissue sarcomas and the subgroups osteosarcoma, rhabdomyosarcoma and Ewing Sarcoma Family of Tumours (ESFT) were considered separately. Significant positive associations were seen between rhabdomyosarcoma and paternal exposure to EMFs (odds ratio = 1.67, CI = 1.22–2.28) and also for ESFT and textile dust (1.93, 1.01–3.63). There were putative protective effects on total bone tumours of paternal dermal exposure to hydrocarbons, metal, metal working or oil mists.

Conclusions

Despite the large size and freedom from bias of this study, our results should be interpreted with caution. Many significance tests were undertaken, and chance findings are to be expected. Nevertheless, our finding of associations between ESFT and paternal exposure to textile dust may support related suggestions in the literature.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1
Fig. 2: Paternal occupational exposures and total risk of childhood soft-tissue sarcomas.
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Stiller, C. Childhood cancer in Britain: incidence, survival, mortality. (Oxford University Press, Oxford, 2007).

  2. 2.

    Colt, J. S. & Blair, A. Parental occupational exposures and risk of childhood cancer. Environ. Health Perspect. 106, 909–925 (1998).

  3. 3.

    Feychting, M., Plato, N., Nise, G. & Ahlbom, A. Paternal occupational exposures and childhood cancer. Environ. Health Perspect. 109, 193–196 (2001).

  4. 4.

    McKinney, P. A., Fear, N. T. & Stockton, D., on behalf of the UK Childhood Cancer Study Investigators. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup. Environ. Med. 60, 901–909 (2003).

  5. 5.

    Olshan, A. F. & van Wijngaarden, E. Paternal occupation and childhood cancer. Adv. Exp. Med. Biol. 518, 147–161 (2003).

  6. 6.

    Draper, G. J., Bithell, J. F., Bunch, K. J., Kendall, G. M., Murphy, M. F. G. & Stiller, C. A. Childhood cancer research in Oxford II: the childhood cancer research group. Br. J. Cancer 119, 763–70. (2018).

  7. 7.

    MacCarthy, A., Bunch, K. J., Fear, N. T., King, J. C., Vincent, T. J. & Murphy, M. F. G. Paternal occupation and retinoblastoma: a case-control study based on data for Great Britain 1962-1999. Occup. Environ. Med. 66, 644–649 (2009).

  8. 8.

    Fear, N. T., Vincent, T. J., King, J. C., MacCarthy, A., Bunch, K. J. & Murphy, M. F. G. Wilms tumour and paternal occupation: an analysis of data from the national registry of childhood tumours. Pediatr. Blood Cancer 53, 28–32 (2009).

  9. 9.

    MacCarthy, A., Bunch, K. J., Fear, N. T., King, J. C., Vincent, T. J. & Murphy, M. F. G. Paternal occupation and neuroblastoma: a case-control study based on cancer registry data for Great Britain 1962-1999. Br. J. Cancer 102, 615–619 (2010).

  10. 10.

    Keegan, T. J., Bunch, K. J., Vincent, T. J., King, J. C., O’Neill, K. A., Kendall, G. M. et al. Case-control study of paternal occupation and risk of childhood leukaemia in Great Britain, 1962-2006. Br. J. Cancer 107, 1652–1659 (2012).

  11. 11.

    Keegan, T. J., Bunch, K. J., Vincent, T. J., King, J. C., O’Neill, K. A., Kendall, G. M. et al. Case-control study of paternal occupation and social class with risk of childhood central nervous system tumours in Great Britain, 1962-2006. Br. J. Cancer 108, 1907–1914 (2013).

  12. 12.

    Bunch, K. J., Kendall, G. M., Stiller, C. A., Vincent, T. J. & Murphy, M. F. G. Case–control study of paternal occupational exposures and childhood lymphoma in Great Britain, 1962–2010. Br. J. Cancer 120, 1153–1161 (2019).

  13. 13.

    Steliarova-Foucher, E., Stiller, C., Lacour, B. & Kaatsch, P. International Classification of Childhood Cancer, third edition. Cancer 103, 1457–1467 (2005).

  14. 14.

    Steliarova-Foucher, E., Colombet, M., Ries, L. A. G., Moreno, F., Dolya, A., Bray, F. et al. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 18, 719–731 (2017). Epub 2017/04/16.

  15. 15.

    Steliarova-Foucher, E., Colombet, M., Ries, L. A. G., Hesseling, P., Moreno, F., Shin, H. Y. et al. International Incidence of Childhood Cancer, Volume III (electronic version). (International Agency for Research on Cancer, Lyon, France, 2017).

  16. 16.

    Kroll, M. E., Carpenter, L. M., Murphy, M. F. G. & Stiller, C. A. Effects of changes in diagnosis and registration on time trends in recorded childhood cancer incidence in Great Britain. Br. J. Cancer 107, 1159–1162 (2012).

  17. 17.

    Parkin, D. M., Stiller, C. A. & Nectoux, J. International variations in the incidence of childhood bone tumours. Int. J. cancer 53, 371–376 (1993).

  18. 18.

    El-Mallawany, N. K., McAtee, C. L., Campbell, L. R. & Kazembe, P. N. Pediatric Kaposi sarcoma in context of the HIV epidemic in sub-Saharan Africa: current perspectives. Pediatr. health, Med. therapeutics 9, 35–46 (2018). Epub 2018/05/04.

  19. 19.

    Steliarova-Foucher, E., Stiller, C., Kaatsch, P., Berrino, F. & Coebergh, J. W., on behalf of the ACCIS Scientific Committee. Trends in childhood cancer incidence in Europe, 1970–99. Lancet 365, 2088 (2005).

  20. 20.

    Burningham, Z., Hashibe, M., Spector, L. & Schiffman, J. D. The epidemiology of sarcoma. Clin. Sarcoma Res. 2, 14 (2012).

  21. 21.

    Thomas, D. M. & Ballinger, M. L. Etiologic, environmental and inherited risk factors in sarcomas. J. Surgical Oncol. 111, 490–495 (2015).

  22. 22.

    Hartley, A. L., Birch, J. M., McKinney, P. A., Teare, M. D., Blair, V., Carrette, J. et al. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): case control study of children with bone and soft tissue sarcomas. Br. J. Cancer 58, 838–842 (1988).

  23. 23.

    Bjørge, T., Sørensen, H. T., Grotmol, T., Engeland, A., Stephansson, O., Gissler, M. et al. Fetal growth and childhood cancer: a population-based study. Pediatrics 132, e1265–e1275 (2013).

  24. 24.

    O’Neill, K. A., Murphy, M. F. G., Bunch, K. J., Puumala, S. E., Carozza, S. E., Chow, E. J. et al. Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases. Int. J. Epidemiol. 44, 153–168 (2015).

  25. 25.

    Morimoto, L. M., McCauley, K., Ma, X., Wiemels, J. L., Chokkalingam, A. P. & Metayer, C. Birth weight, fetal growth, and risk of pediatric rhabdomyosarcoma: an updated record linkage study in California. Ann. Epidemiol. 26, 141–145 (2016).

  26. 26.

    Lupo, P. J., Danysh, H. E., Skapek, S. X., Hawkins, D. S., Spector, L. G., Zhou, R. et al. Maternal and birth characteristics and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group. Cancer Causes Control 25, 905–913 (2014).

  27. 27.

    Troisi, R., Stephansson, O., Jacobsen, J., Tretli, S., Sorensen, H. T., Gissler, M. et al. Perinatal characteristics and bone cancer risk in offspring–a Scandinavian population-based study. Acta Oncol. 53, 830–838 (2014).

  28. 28.

    PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Soft Tissue Sarcoma Treatment. Bethesda MD: National Cancer Institute; 2019 [updated 06/04/2019; cited 2019 21 June 2019]; Available from: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-soft-tissue-treatment-pdq.

  29. 29.

    Lupo P., E. Luna-Gierke R., M. Chambers T., Tavelin B., E. Scheurer M., Melin B., et al. Perinatal and familial risk factors for soft tissue sarcomas in childhood through young adulthood: a population-based assessment in 4 million live births. Int. J. Cancer. 146, 791–802 (2019).

  30. 30.

    Mirabello, L., Pfeiffer, R., Murphy, G., Daw, N. C., Patiño-García, A., Troisi, R. J. et al. Height at diagnosis and birth-weight as risk factors for osteosarcoma. Cancer causes Control.: CCC 22, 899–908 (2011).

  31. 31.

    Berrington de Gonzalez, A., Kutsenko, A. & Rajaraman, P. Sarcoma risk after radiation exposure. Clin. Sarcoma Res. 2, 18 (2012).

  32. 32.

    Preston, D. L., Ron, E., Tokuoka, S., Funamoto, S., Nishi, N., Soda, M. et al. Solid cancer incidence in atomic bomb survivors: 1958-1998. Radiat. Res. 168, 1–64 (2007).

  33. 33.

    Samartzis, D., Nishi, N., Hayashi, M., Cologne, J., Cullings, H. M., Kodama, K. et al. Exposure to ionizing radiation and development of bone sarcoma: new insights based on atomic-bomb survivors of Hiroshima and Nagasaki. J. Bone Joint Surg. Am. 93, 1008–1015 (2011).

  34. 34.

    Rubino, C., Shamsaldin, A., Le, M. G., Labbe, M., Guinebretiere, J. M., Chavaudra, J. et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res. Treat. 89, 277–288 (2005).

  35. 35.

    Samartzis, D., Nishi, N., Cologne, J., Funamoto, S., Hayashi, M. Kodama, K. et al. Ionizing radiation exposure and the development of soft-tissue sarcomas in atomic-bomb survivors. J. Bone Joint Surg. Am. 95, 222–229 (2013).

  36. 36.

    Magnani, C., Pastore, G., Luzzatto, L., Carli, M., Lubrano, P. & Terracini, B. Risk factors for soft tissue sarcomas in childhood: a case-control study. Tumori 75, 396–400 (1989).

  37. 37.

    Committee to Coordinate Environmental Health and Related Programs. Public Health Service report on fluoride benefits and risks. MMWR Recomm. Rep. 40, 1–8 (1991).

  38. 38.

    Blakey, K., Feltbower, R. G., Parslow, R. C., James, P. W., Gómez Pozo, B., Stiller, C. et al. Is fluoride a risk factor for bone cancer? Small area analysis of osteosarcoma and Ewing sarcoma diagnosed among 0–49-year-olds in Great Britain, 1980–2005. Int. J. Epidemiol. 43, 224–234 (2014).

  39. 39.

    Paltiel, O., Tikellis, G., Linet, M., Golding, J., Lemeshow, S., Phillips, G. et al. Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C). Paediatr. Perinat. Epidemiol. 29, 335–345 (2015).

  40. 40.

    Savitz, D. A. & Chen, J. Parental occupation and childhood cancer: review of epidemiologic studies. Environ. Health Perspect. 88, 325–337 (1990).

  41. 41.

    Hum, L., Kreiger, N. & Finkelstein, M. M. The relationship between parental occupation and bone cancer risk in offspring. Int J. Epidemiol. 27, 766–771 (1998).

  42. 42.

    Olsen, J. H., de Nully Brown, P., Schulgen, G. & Jensen, O. M. Parental employment at time of conception and risk of cancer in offspring. Eur. J. Cancer. 27, 958–965 (1991).

  43. 43.

    Gelberg, K. H., Fitzgerald, E. F., Hwang, S. & Dubrow, R. Growth and development and other risk factors for osteosarcoma in children and young adults. Int J. Epidemiol. 26, 272–278 (1997).

  44. 44.

    Valery, P. C., McWhirter, W., Sleigh, A., Williams, G. & Bain, C. Farm exposures, parental occupation, and risk of Ewing’s sarcoma in Australia: a national case-control study. Cancer causes Control.: CCC 13, 263–270 (2002).

  45. 45.

    Valery, P. C., Williams, G., Sleigh, A. C., Holly, E. A., Kreiger, N. & Bain, C. Parental occupation and Ewing’s sarcoma: Pooled and meta-analysis. Int. J. Cancer 115, 799–806 (2005).

  46. 46.

    Winn, D. M., Li, F. P., Robison, L. L., Mulvihill, J. J., Daigle, A. E. & Fraumeni, J. F. A case-control study of the etiology of Ewing’s sarcoma. Cancer Epidemiol., Biomark. Prev. 1, 525–532 (1992).

  47. 47.

    Moore, L. E., Gold, L., Stewart, P. A., Gridley, G., Prince, J. R. & Hoar Zahm, S. Parental occupational exposures and Ewing’s sarcoma. Int. J. cancer 114, 472–478 (2005).

  48. 48.

    Zahm, S. H. & Ward, M. H. Pesticides and childhood cancer. Environ. Health Perspect. 106, 893–908 (1998).

  49. 49.

    Infante-Rivard C. & Weichenthal S. Pesticides and childhood cancer: an update of Zahm and Ward’s 1998 review. J Toxicol Environ Health B Crit Rev. 10, 81–99 (2007).

  50. 50.

    Vinson, F., Merhi, M., Baldi, I., Raynal, H. & Gamet-Payrastre, L. Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies. Occup. Environ. Med. 68, 694–702 (2011).

  51. 51.

    Grufferman, S., Lupo, P. J., Vogel, R. I., Danysh, H. E., Erhardt, E. B. & Ognjanovic, S. Parental military service, agent orange exposure, and the risk of rhabdomyosarcoma in offspring. J. Pediatrics 165, 1216–1221 (2014).

  52. 52.

    Pearce, M. S., Hammal, D. M., Dorak, M. T., McNally, R. J. Q. & Parker, L. Paternal occupational exposure to electro-magnetic fields as a risk factor for cancer in children and young adults: a case-control study from the North of England. Pediatr. Blood Cancer 49, 280–286 (2007).

  53. 53.

    Pannett, B., Coggon, D. & Acheson, E. D. A job-exposure matrix for use in population based studies in England and Wales. Br. J. Ind. Med. 42, 777 (1985).

  54. 54.

    Kroll, M. E., Murphy, M. F. G., Carpenter, L. M. & Stiller, C. A. Childhood cancer registration in Britain: capture-recapture estimates of completeness of ascertainment. Br. J. Cancer 104, 1227–1233 (2011).

  55. 55.

    Stiller, C. A. & Bose, S. Estimated completeness of ascertainment for childhood cancer in the UK 2005–2010. (National Cancer Intelligence Network, London, 2013). [updated 2013].

  56. 56.

    Office of Population Censuses & Surveys. Classification of Occupations 1980. (HMSO, London, 1980).

  57. 57.

    Fear, N., Roman, E., Reeves, G. & Pannett, B. Father’s occupation and childhood mortality: analysis of routinely collected data. Health Stat. Q. 2, 7–15 (1999).

  58. 58.

    Office of Population Censuses & Surveys. Classification of Occupations 1970. (HMSO, London, 1970).

  59. 59.

    Simpson, J., Roman, E., Law, G. & Pannett, B. Women’s occupation and cancer: Preliminary analysis of cancer registrations in England and Wales, 1971–1990. Am. J. Ind. Med. 36, 172–185 (1999).

  60. 60.

    Fear, N. T., Roman, E., Reeves, G. & Pannett, B. Are the children of fathers whose jobs involve contact with many people at an increased risk of leukaemia? Occup. Environ. Med. 56, 438–442 (1999).

  61. 61.

    ONS Classification and Harmonisation Unit. CO80 simplified 1980 occupation classification ONS factsheet. Crown Copyright; 1985.

  62. 62.

    Breslow, N. E. & Day, N. E. Statistical Methods in Cancer Research Volume 1 - The Analysis of Case-Control Studies IARC Scientific Publications No.32. (International Agency for Research on Cancer, Lyon, 1980).

  63. 63.

    World Health Organization. Cancer: Causes, Occurrence and Control IARC Scientific Publications No.100. (IARC, Lyon, 1990).

  64. 64.

    Bland, J. M. & Altman, D. G. Multiple significance tests: the Bonferroni method. BMJ 310, 170 (1995).

  65. 65.

    Schüz, J., Spector, L. G. & Ross, J. A. Bias in studies of parental self-reported occupational exposure and childhood cancer. Am. J. Epidemiol. 158, 710–716 (2003).

  66. 66.

    Marsden, H. B. & Steward, J. K. Ewings tumours and neuroblastomas. J. Clin. Pathol. 17, 411 (1964).

  67. 67.

    McKinney, P. A., Alexander, F. E., Nicholson, C., Cartwright, R. A. & Carrette, J. Mothers’ reports of childhood vaccinations and infections and their concordance with general practitioner records. J. Public Health Med. 13, 13–22 (1991).

  68. 68.

    Olshan, A. F. & Daniels, J. L. Invited commentary: Pesticides and childhood cancer. Am. J. Epidemiol. 151, 647–649 (2000).

  69. 69.

    Kendall, G. M., Little, M. P., Wakeford, R., Bunch, K. J., Miles, J. C. H., Vincent, T. J. et al. A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006. Leukemia 27, 3–9 (2013).

  70. 70.

    Carstairs, V. & Morris, R. Deprivation and Health in Scotland. (Aberdeen University Press, Aberdeen, 1991).

Download references

Acknowledgements

We acknowledge the major contributions made by Nicola Fear, Tom Keegan and Angela MacCarthy to earlier papers in this series. We are grateful to Janette King for her work on occupational coding and to Helen Elwell of BMA Library Services for conducting a computerised literature search on our behalf.

Author information

Affiliations

Authors

Contributions

Study design: M.F.G.M., T.J.V. and K.J.B. Data assembly and analysis: K.J.B. and T.J.V. Initial draft of the paper: G.M.K., K.J.B. and C.A.S. All authors contributed to interpretation of the results, revision to and final approval of the paper. All authors take responsibility for the integrity of the data and accuracy of the analysis.

Corresponding author

Correspondence to Gerald M. Kendall.

Ethics declarations

Ethics approval and consent to participate

Oxfordshire Research Ethics Committee (Oxfordshire REC C, Ref 12/SC/0532) approved the use of these data in 2012 without the need for individual subject consent.

Consent to publish

Not applicable.

Data availability

The data are contained within the National Registry of Childhood Tumours.

Competing interests

The authors declare no competing interests.

Funding information

The work of the Childhood Cancer Research Group (CCRG) was supported by Children with Cancer UK, the Scottish Government and the Department of Health for England and Wales.

Additional information

Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kendall, G.M., Bunch, K.J., Stiller, C.A. et al. Case–control study of paternal occupational exposures and childhood bone tumours and soft-tissue sarcomas in Great Britain, 1962–2010. Br J Cancer 122, 1250–1259 (2020). https://doi.org/10.1038/s41416-020-0760-7

Download citation