title: Risk of thyroid cancer in first-degree relatives of patients with non-medullary thyroid cancer by histology type and age at diagnosis: a joint study from five Nordic countries.
abstract: BACKGROUND
  We aimed to estimate lifetime cumulative risk of thyroid cancer (CRTC) in first-degree relatives of patients with non-medullary thyroid cancers (NMTC), including papillary (PTC)/follicular/oxyphilic/anaplastic thyroid carcinoma, by histology and age at diagnosis in patients and their relatives.
  
  
  METHODS
  A population-based cohort of 63 495 first-degree relatives of 11 206 NMTC patients diagnosed in 1955-2009 in Nordic countries was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated using histology-specific, age-specific, sex-specific, period-specific and country-specific incidence rates as reference.
  
  
  RESULTS
  The 0-84-year CRTC in female relatives of a patient with PTC was 2%, representing a threefold increase over the general population risk (SIR=2.9, 95% CI 2.4 to 3.4; Men: CRTC=1%, SIR=2.5, 95% CI 1.9 to 3.3). When there were ≥2 PTC patients diagnosed at age <60 years in a family, CRTC for female relatives was 10% (male 24%). Twins had a 23-fold increased risk of concordant PTC. Family history of follicular/oxyphilic/anaplastic carcinoma increased CRTC in relatives to about 1-2%. Although no familial case of concordant oxyphilic/anaplastic carcinoma was found, familial risks of discordant histology types of NMTC were interchangeably high for most of the types, for example, higher risk of PTC when a first-degree relative had follicular (SIR=3.0, 95%CI 1.7 to 4.9) or anaplastic (SIR=3.6, 95% CI 1.2 to 8.4) carcinoma. The earlier a patient was diagnosed with PTC in a family, the higher was the SIR in his/her younger relatives. There was a tendency towards concordant age at diagnosis of thyroid cancer among relatives of PTC patients.
  
  
  CONCLUSIONS
  This study provides clinically relevant risk estimates for family members of NMTC patients.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg 69120, Germany. m.fallah@dkfz.de
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fallah
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.forename: Jörgen H
authors.initials: JH
authors.lastname: Olsen
authors.forename: Steinar
authors.initials: S
authors.lastname: Tretli
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012306:Risk; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D012737:Sex Factors; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
keywords: Familial risk; Nordic countries; Thyroid cancer; cumulative risk; non-medullary thyroid carcinoma