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 Morey Lindor, John L. Hopper, Mark A. Jenkins, Aung Ko Win

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)545-551
Number of pages7
JournalFamilial Cancer
Volume14
Issue number4
DOIs
StatePublished - May 12 2015

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Neoplasms
DNA Mismatch Repair
Colorectal Neoplasms
Genes
Germ-Line Mutation
Endometrial Neoplasms
Brain Neoplasms
Colonic Neoplasms
Population
Registries
Central Nervous System

Keywords

  • Childhood cancer
  • Familial cancer
  • Lynch syndrome
  • Mismatch repair

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)

Cite this

Heath, J. A., Reece, J. C., Buchanan, D. D., Casey, G., Durno, C. A., Gallinger, S., ... Win, A. K. (2015). Childhood cancers in families with and without Lynch syndrome. Familial Cancer, 14(4), 545-551. https://doi.org/10.1007/s10689-015-9810-3

Childhood cancers in families with and without Lynch syndrome. / Heath, John A.; Reece, Jeanette C.; Buchanan, Daniel D.; Casey, Graham; Durno, Carol A.; Gallinger, Steven; Haile, Robert W.; Newcomb, Polly A.; Potter, John D.; Thibodeau, Stephen N; Le Marchand, Loïc; Lindor, Noralane Morey; Hopper, John L.; Jenkins, Mark A.; Win, Aung Ko.

In: Familial Cancer, Vol. 14, No. 4, 12.05.2015, p. 545-551.

Research output: Contribution to journalArticle

Heath, JA, Reece, JC, Buchanan, DD, Casey, G, Durno, CA, Gallinger, S, Haile, RW, Newcomb, PA, Potter, JD, Thibodeau, SN, Le Marchand, L, Lindor, NM, Hopper, JL, Jenkins, MA & Win, AK 2015, 'Childhood cancers in families with and without Lynch syndrome', Familial Cancer, vol. 14, no. 4, pp. 545-551. https://doi.org/10.1007/s10689-015-9810-3
Heath JA, Reece JC, Buchanan DD, Casey G, Durno CA, Gallinger S et al. Childhood cancers in families with and without Lynch syndrome. Familial Cancer. 2015 May 12;14(4):545-551. https://doi.org/10.1007/s10689-015-9810-3
Heath, John A. ; Reece, Jeanette C. ; Buchanan, Daniel D. ; Casey, Graham ; Durno, Carol A. ; Gallinger, Steven ; Haile, Robert W. ; Newcomb, Polly A. ; Potter, John D. ; Thibodeau, Stephen N ; Le Marchand, Loïc ; Lindor, Noralane Morey ; Hopper, John L. ; Jenkins, Mark A. ; Win, Aung Ko. / Childhood cancers in families with and without Lynch syndrome. In: Familial Cancer. 2015 ; Vol. 14, No. 4. pp. 545-551.
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