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Childhood cancers in families with and without Lynch syndrome

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Abstract

Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR-deficient colorectal cancer (non-Lynch syndrome families). There was no evidence of a difference in the proportion of relatives with a childhood cancer between Lynch syndrome families (41/17,230; 0.24 %) and non-Lynch syndrome families (179/94,302; 0.19 %; p = 0.19). Incidence rate of all childhood cancers was estimated to be 147 (95 % CI 107–206) per million population per year in Lynch syndrome families and 115 (95 % CI 99.1–134) per million population per year in non-Lynch syndrome families. There was no evidence for a significant increase in the risk of all childhood cancers, hematologic cancers, brain and central nervous system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch syndrome families compared with non-Lynch syndrome families. Larger studies, however, are required to more accurately define the risk of specific individual childhood cancers in Lynch syndrome families.

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Acknowledgments

The authors thank all study participants of the Colon Cancer Family Registry and staff for their contributions to this project. This work was supported by Grant UM1 CA167551 from the National Cancer Institute, National Institutes of Health and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centers include Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), Stanford Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), and University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). JAH is an Australian National Health and Medical Research Council (NHMRC) Career Development Fellow. MAJ is a NHMRC Senior Research Fellow. JLH is a NHMRC Senior Principal Research Fellow. AKW is an NHMRC Early Career Fellow. DDB is a University of Melbourne Research at Melbourne Accelerator Program (R@MAP) Senior Research Fellow.

Conflict of interest

The authors have no conflict of interest to declare with respect to this manuscript.

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Authors and Affiliations

  1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia

    John A. Heath, Jeanette C. Reece, Daniel D. Buchanan, John L. Hopper, Mark A. Jenkins & Aung Ko Win

  2. Department of Oncology, Sidra Medical and Research Center, Doha, Qatar

    John A. Heath

  3. Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

    Daniel D. Buchanan

  4. Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Graham Casey

  5. Familial Gastrointestinal Cancer Registry, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada

    Carol A. Durno

  6. Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

    Carol A. Durno

  7. Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Carol A. Durno

  8. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Steven Gallinger

  9. Division of Oncology, Department of Medicine, Stanford University, Los Angeles, CA, USA

    Robert W. Haile

  10. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Polly A. Newcomb & John D. Potter

  11. School of Public Health, University of Washington, Seattle, WA, USA

    Polly A. Newcomb & John D. Potter

  12. Centre for Public Health Research, Massey University, Wellington, New Zealand

    John D. Potter

  13. Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Stephen N. Thibodeau

  14. University of Hawaii Cancer Center, Honolulu, HI, USA

    Loïc Le Marchand

  15. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA

    Noralane M. Lindor

  16. Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea

    John L. Hopper

  17. Institute of Health and Environment, Seoul National University, Seoul, Korea

    John L. Hopper

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  1. John A. Heath
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  2. Jeanette C. Reece
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  3. Daniel D. Buchanan
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  4. Graham Casey
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  5. Carol A. Durno
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  6. Steven Gallinger
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  7. Robert W. Haile
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  8. Polly A. Newcomb
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  9. John D. Potter
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  10. Stephen N. Thibodeau
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  11. Loïc Le Marchand
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  12. Noralane M. Lindor
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  13. John L. Hopper
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  14. Mark A. Jenkins
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  15. Aung Ko Win
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Corresponding author

Correspondence to Aung Ko Win.

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Disclaimer The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Colon Cancer Family Registry. Authors had full responsibility for the design of the study, the collection of the data, the analysis and interpretation of the data, the writing of the manuscript and the decision to submit the manuscript for publication.

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Heath, J.A., Reece, J.C., Buchanan, D.D. et al. Childhood cancers in families with and without Lynch syndrome. Familial Cancer 14, 545–551 (2015). https://doi.org/10.1007/s10689-015-9810-3

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