Familial Cancer

, Volume 14, Issue 4, pp 545–551 | Cite as

Childhood cancers in families with and without Lynch syndrome

  • John A. Heath
  • Jeanette C. Reece
  • Daniel D. Buchanan
  • Graham Casey
  • Carol A. Durno
  • Steven Gallinger
  • Robert W. Haile
  • Polly A. Newcomb
  • John D. Potter
  • Stephen N. Thibodeau
  • Loïc Le Marchand
  • Noralane M. Lindor
  • John L. Hopper
  • Mark A. Jenkins
  • Aung Ko WinEmail author
Original Article


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.


Childhood cancer Familial cancer Lynch syndrome Mismatch repair 



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.

Supplementary material

10689_2015_9810_MOESM1_ESM.xlsx (13 kb)
Supplementary material 1 (XLSX 12 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • John A. Heath
    • 1
    • 2
  • Jeanette C. Reece
    • 1
  • Daniel D. Buchanan
    • 1
    • 3
  • Graham Casey
    • 4
  • Carol A. Durno
    • 5
    • 6
    • 7
  • Steven Gallinger
    • 8
  • Robert W. Haile
    • 9
  • Polly A. Newcomb
    • 10
    • 11
  • John D. Potter
    • 10
    • 11
    • 12
  • Stephen N. Thibodeau
    • 13
  • Loïc Le Marchand
    • 14
  • Noralane M. Lindor
    • 15
  • John L. Hopper
    • 1
    • 16
    • 17
  • Mark A. Jenkins
    • 1
  • Aung Ko Win
    • 1
    Email author
  1. 1.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthUniversity of MelbourneMelbourneAustralia
  2. 2.Department of OncologySidra Medical and Research CenterDohaQatar
  3. 3.Oncogenomics Group, Genetic Epidemiology Laboratory, Department of PathologyThe University of MelbourneParkvilleAustralia
  4. 4.Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Familial Gastrointestinal Cancer Registry, Zane Cohen Centre for Digestive DiseasesMount Sinai HospitalTorontoCanada
  6. 6.Department of Surgery, Mount Sinai HospitalTorontoCanada
  7. 7.Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  8. 8.Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalUniversity of TorontoTorontoCanada
  9. 9.Division of Oncology, Department of MedicineStanford UniversityLos AngelesUSA
  10. 10.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  11. 11.School of Public HealthUniversity of WashingtonSeattleUSA
  12. 12.Centre for Public Health ResearchMassey UniversityWellingtonNew Zealand
  13. 13.Molecular Genetics Laboratory, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  14. 14.University of Hawaii Cancer CenterHonoluluUSA
  15. 15.Department of Health Science ResearchMayo Clinic ArizonaScottsdaleUSA
  16. 16.Department of Epidemiology, School of Public HealthSeoul National UniversitySeoulKorea
  17. 17.Institute of Health and EnvironmentSeoul National UniversitySeoulKorea

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