Quantification of thyroid cancer and multinodular goiter risk in the DICER1 syndrome: a family-based cohort study.

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Quantification of thyroid cancer and multinodular goiter risk in the DICER1 syndrome: a family-based cohort study.

J Clin Endocrinol Metab. 2017 Feb 02;:

Authors: Khan NE, Bauer AJ, Schultz KA, Doros L, Decastro RM, Ling A, Lodish MB, Harney LA, Kase RG, Carr AG, Rossi CT, Field A, Harris AK, Williams GM, Dehner LP, Messinger YH, Hill DA, Stewart DR

Abstract
Context: The risk of thyroid cancer and multinodular goiter (MNG) in the DICER1 syndrome, a rare tumor-predisposition disorder, is unknown.
Objective: To quantify the risk of thyroid cancer and MNG in individuals with the DICER1 syndrome.
Design: Family-based cohort study.
Setting: National Institutes of Health (NIH) Clinical Center (CC).
Participants: The National Cancer Institute DICER1 syndrome cohort consisted of 145 individuals with a DICER1 germline mutation and 135 family controls from 48 families.
Interventions: Each individual completed a detailed medical history questionnaire. A subset underwent a 3-day evaluation at the NIH CC.
Main Outcome Measures: The cumulative incidence of MNG (or thyroidectomy) was quantified using the complement of the Kaplan-Meier product limit estimator. We compared the observed number of thyroid cancers in the NCI DICER1 cohort with matched data from the Surveillance, Epidemiology and End Results (SEER) Program. We performed germline and somatic (thyroid cancer, MNG) DICER1 sequencing.
Results: By age 40 years, the cumulative incidence of MNG or thyroidectomy was 75% in women and 17% in men with the DICER1 syndrome, compared with 8% control women (P < 0.001) and 0% control men (P = 0.0096). During 3,937 person-years of observation, individuals with the DICER1 syndrome were at 16-fold increased risk of thyroid cancer (95%CI=4.3-41; P<0.05), compared with SEER rates. 16/19 (84%) MNG nodules and 3/3 thyroid cancers harbored germline and somatic pathogenic DICER1 mutations.
Conclusions: We propose a model of thyroid carcinogenesis in the DICER1 syndrome. Early-onset, familial or male MNG should prompt consideration of the DICER1 syndrome.

PMID: 28323992 [PubMed - as supplied by publisher]

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