title: Childhood cancers in families with and without Lynch syndrome.
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.
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia.|Department of Oncology, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: John A
authors.initials: JA
authors.lastname: Heath
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Reece
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia.|Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Familial Gastrointestinal Cancer Registry, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.|Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada.|Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Durno
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, Los Angeles, CA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|School of Public Health, University of Washington, Seattle, WA, USA.|Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia.|Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea.|Institute of Health and Environment, Seoul National University, Seoul, Korea.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, 3010, Australia. awin@unimelb.edu.au.
authors.forename: Aung Ko
authors.identifier: http://orcid.org/0000-0002-2794-5261
authors.initials: AK
authors.lastname: Win
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics*; D001315:Australia / Q000453:epidemiology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D000071858:Epithelial Cell Adhesion Molecule; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D011379:Prognosis; D012042:Registries; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D045643:DNA Repair Enzymes
keywords: Childhood cancer; Familial cancer; Lynch syndrome; Mismatch repair