Childhood cancers in families with and without Lynch syndrome

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 w...

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Bibliographic Details
Published in:Familial cancer 2015-12, Vol.14 (4), p.545-551
Main Authors: 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 M., Hopper, John L., Jenkins, Mark A., Win, Aung Ko
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antigens, Neoplasm - genetics
Australia - epidemiology
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Adhesion Molecules - genetics
Child
Colorectal Neoplasms, Hereditary Nonpolyposis - complications
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
DNA Repair Enzymes - genetics
Epidemiology
Epithelial Cell Adhesion Molecule
Family
Female
Follow-Up Studies
Genetic Predisposition to Disease
Germ-Line Mutation - genetics
Human Genetics
Humans
Incidence
Male
Neoplasms, Second Primary - epidemiology
Neoplasms, Second Primary - etiology
Original Article
Prognosis
Registries
Young Adult
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Summary: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.
ISSN:1389-9600
1573-7292
DOI:10.1007/s10689-015-9810-3