Title |
Penetrance of a rare familial mutation predisposing to papillary thyroid cancer
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Published in |
Familial Cancer, October 2017
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DOI | 10.1007/s10689-017-0048-0 |
Pubmed ID | |
Authors |
Donika Saporito, Pamela Brock, Heather Hampel, Jennifer Sipos, Soledad Fernandez, Sandya Liyanarachchi, Albert de la Chapelle, Rebecca Nagy |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 33% |
United States | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Scientists | 1 | 33% |
Members of the public | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Unspecified | 3 | 23% |
Researcher | 2 | 15% |
Student > Bachelor | 1 | 8% |
Student > Doctoral Student | 1 | 8% |
Student > Master | 1 | 8% |
Other | 1 | 8% |
Unknown | 4 | 31% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 31% |
Unspecified | 3 | 23% |
Agricultural and Biological Sciences | 1 | 8% |
Biochemistry, Genetics and Molecular Biology | 1 | 8% |
Unknown | 4 | 31% |