Familial Cancer

, Volume 17, Issue 3, pp 431–434 | Cite as

Penetrance of a rare familial mutation predisposing to papillary thyroid cancer

  • Donika Saporito
  • Pamela Brock
  • Heather Hampel
  • Jennifer Sipos
  • Soledad Fernandez
  • Sandya Liyanarachchi
  • Albert de la Chapelle
  • Rebecca Nagy
Short Communication


Familial non-medullary thyroid cancer (FNMTC) is clinically defined as two or more first-degree relatives with NMTC and appears to follow an autosomal dominant inheritance pattern. Approximately 5–7% of NMTC is hereditary and affects multiple generations with a young age of onset. The primary aim of this study was to determine the age-specific penetrance of NMTC in individuals from a large family with FNMTC with a previously identified private mutation at 4q32, with a secondary aim to determine the penetrance for benign thyroid disease in this family. We present a large family with NMTC in which we had previously described a culpable mutation. Participants provided their personal medical history and family history. The germline 4q32 A > C mutation was detected in 34 of 68 tested individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease was determined using the inverted Kaplan–Meier method of segregation analysis. Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5–88.7) risk of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0–83.8) risk of developing benign thyroid disease by age 70. The 4q32 A > C mutation significantly increases the risk to develop thyroid cancer but not benign thyroid disease in members of this family. The female:male sex ratio of 1.33 that we observed in affected mutation carriers differs greatly from the ratio of approximately 3:1 observed in PTC, supporting a central role of the mutation. Early thyroid surveillance with annual ultrasound is recommended to individuals testing positive for this private familial mutation.


Familial non-medullary thyroid cancer Papillary thyroid cancer Anaplastic thyroid cancer Penetrance Benign thyroid disease Risk 



We thank members of the de la Chapelle team for their dedication to this research as well as The Ohio State University faculty and staff for their support. This work was funded by National Cancer Institute Grants P01 CA124570 and P30 CA16058.

Compliance with ethical standards

Conflict of interest

No competing financial interests exist.

Supplementary material

10689_2017_48_MOESM1_ESM.docx (89 kb)
Supplementary material 1 (DOCX 89 KB)


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Department of Clinical Cancer GeneticsMD Anderson Cancer CenterHoustonUSA
  2. 2.Division of Human GeneticsThe Ohio State University Wexner Medical CenterColumbusUSA
  3. 3.Division of Human Genetics, Department of Internal Medicine and the Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  4. 4.Division of Endocrinology, Diabetes and MetabolismThe Ohio State University Wexner Medical CenterColumbusUSA
  5. 5.Department of Biomedical InformaticsThe Ohio State University Wexner Medical CenterColumbusUSA
  6. 6.Department of Cancer Biology and Genetics and the Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  7. 7.Senior Medical Science LiaisonGuardant HealthRedwood CityUSA

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