Prevalence of thyroid diseases in familial adenomatous polyposis: a systematic review and meta-analysis

Abstract

Thyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its exact prevalence is not well established and recent studies have shown an increasing number of TC in this patient population. The prevalence of benign thyroid masses and endocrinologic thyroid disorders are also poorly described. We conducted a systematic review and meta-analysis by using a random-effects model to characterize TC and estimated the prevalence of thyroid diseases in FAP patients. Twelve studies (n = 9821) were included. Pooled prevalence of TC, benign thyroid masses, and endocrinologic thyroid disorders in FAP were 2.6% [95% confidence interval (CI) 1.3-4.8], 48.8% [95% CI 33.8-64.0], and 6.9% [95% CI 4.5-10.3] respectively. Subgroup analyses revealed higher prevalence of TC in studies with fewer participants, studies that used screening ultrasound to diagnose TC, and studies that were published after 2002. TC diagnosis preceded the diagnosis of FAP in 34% of the patients. The means age at diagnosis of FAP and TC were 29 and 31 years, respectively. 95% of the patients were female and the most common pathology was of papillary subtype (83.3%). Most mutations (79.2%) were located at the 5' end of APC gene. In summary, benign thyroid disorders are common in FAP, yet, TC is an uncommon phenomenon. Certain patient subset, such as young female with APC mutation at the 5' end, might benefit from routine surveillance ultrasound.

Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona, June 2018

“…Abdominal ultrasound can be proposed, initially for hepatoblastoma (until the age of 5 years), later for detection of desmoids [26,33,44,47]. Annual thyroid ultrasound can be offered to women, starting at the age of 15 years [48]. Surveillance for PC should be performed if there is a family history of PC and is analogous to PC surveillance in LS patients (see section 3.1.9).…”

A unique case of two somatic APC mutations in an early onset cribriform-morular variant of papillary thyroid carcinoma and overview of the literature

“…Of the reported 36 germline APC variants, 4 occurred in and 31 before the MCR (one of the germline variants was a whole gene deletion) (Table 1). However, all germline APC variants (Table 1) were within the region extending from codons 140 to 1309, that has been associated to PTC in terms of genotype-phenotype correlations of extra-intestinal manifestations of FAP [39,53,54]. Of the 17 reported somatic APC variants (Table 1), 3 variants were out of and 14 variants were in this region (codons 140-1309), as well as the two somatic APC variants identified in the index patient.…”

Genetic susceptibility to hereditary non-medullary thyroid cancer

“…The prevalence of thyroid cancer among patients with FAP is 2.6%. These thyroid cancers have a unique cribriform pattern on histologic examination and occur more commonly at a young age (< 30 years) in women (95%) [ 112 , 113 ].…”

“…The prevalence of thyroid cancer among patients with FAP is 2.6%. These thyroid cancers have a unique cribriform pattern on histologic examination and occur more commonly at a young age (< 30 years) in women (95%) [112,113]. More than 60% of APC pathogenic mutations have been identified in the mutation cluster region between codons 1284 and 1580 [114,115].…”