ABSTRACT
<p><b>Background</b>The first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease.</p><p><b>Methods:</b>We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members.</p><p><b>Results:</b>The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan-Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045).</p><p><b>Conclusions:</b>Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC.</p>
ABSTRACT
Familial nonmedullary thyroid carcinoma means to two or more first-degree relatives of the family with NMTC,in the absence of other known family syndromes (such as Gardner's syndrome,Cowden disease,Carney complex,Werner syndrome,and so on),and common thyroid cancer risk factors including the neck radiation and iodine deficiency,and so on.The genes involved in the pathogenesis of familial nonmedullary thyroid carcinoma (FNMTC) are yet to be elucidated,although some recent studies identified several predisposition loci with a high degree of genetic heterogeneity.Several studies demonstrated that patients with FNMTC have increased rates of multifocal disease,extrathyroidal invasion,and involved lymph nodes compared with sporadic disease.It has been hypothesized that this increased aggressiveness translates into higher recurrence rates and decreased survival of patients with FNMTC.
ABSTRACT
Familial non-medullary thyroid cancer (FNMTC) may be considered as a separate clinical entity with variable aggressive biologic behaviors on the basis of previously published studies. Therefore, a family history of NMTC should be carefully considered as a possible prognostic factor when endocrine surgeons set a plan regarding the extent of surgery, radioactive iodine treatment, and follow-up strategy for FNMTC patients.
Subject(s)
Humans , Iodine , Thyroid NeoplasmsABSTRACT
Familial non-medullary thyroid carcinoma (FNMTC) is de fi ned as the presence of two or more affected fi rst-degree relatives with non-medullary thyroid cancers without other known familial syndromes. FNMTC is one of the most inheritable forms of all cancers, with a high risk of a first-degree relative developing the disease. Compared with sporadic non-medullary thyroid carcinoma (NMTC), FNMTC presents at a younger age and is associated with a higher incidence of multifocal disease and metastasis. This in-creased aggressiveness has been hypothesized to translate into higher recurrence rates and decreased survival of patients with FNMTC. The genes involved in the pathogenesis of FNMTC are yet to be elucidated, although some recent studies identified several predisposi-tion loci with a high degree of genetic heterogeneity. Since 2005, next-generation sequencing (NGS) technologies have been developing as rapid, high-throughput, and cost-effective approaches to fulfill medical sciences and research demands. With the use of NGS, the un-derlying causative genes can be directly distinguished via systematic filtering, through which the identified gene variants are verified for novelty and functionality.
ABSTRACT
OBJECTIVE: To evaluate the frequency of thyroid cancer and thyroid dysfunction in first-degree relatives of thyroid cancer patients, and to determine if there is a difference between familial and sporadic thyroid cancer. SUBJECTS AND METHODS: Fifteen first-degree relatives of seven families with at least two family members with thyroid cancer (TC) were compared with 128 first-degree relatives of 45 families with only one family member affected. Laboratory and ultrasound evaluation, fine-needle aspiration biopsy and thyroid surgery were used as normally done in clinical practice. RESULTS: Thyroid dysfunction was similar between the two groups. The frequency of TC and autoimmunity in the group that had two relatives with known thyroid cancer was higher, compared with the families that had sporadic thyroid cancer among their family members (40 percent vs. 2 percent, p = 0.0001). CONCLUSION: Frequency of TC increases when more than one member of the family is affected. These findings suggest that these relatives should be screened more frequently than individuals in families in which only one case of TC is observed.
OBJETIVO: Avaliar a frequência de carcinoma de tireoide e disfunção tireoidiana em parentes de pacientes com câncer da tireoide e determinar se há diferença entre aqueles com mais de um familiar acometido e os casos esporádicos. SUJEITO E MÉTODOS: Quinze familiares de sete famílias com dois membros sabidamente acometidos foram submetidos à avaliação ultrassonográfica e laboratorial. Cento e vinte e oito familiares de pacientes com carcinoma de tireoide, porém sem outros casos na família, foram utilizados como grupo comparador. RESULTADOS: Em relação à disfunção tireoidiana, não houve diferença entre os grupos. A frequência de carcinoma da tireoide e autoimunidade foi maior nos parentes que tinham dois membros da família afetados (40 por cento vs. 2 por cento, p = 0.0001). A apresentação clínica foi semelhante nos dois grupos. CONCLUSÃO: Devido à maior frequência de carcinoma de tireoide em parentes que possuem mais de um familiar afetado, o rastreamento desses indivíduos talvez deva ser mais intenso do que nos casos em que há apenas um caso na família.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Carcinoma, Papillary/epidemiology , Thyroid Neoplasms/epidemiology , Autoimmunity , Biopsy, Fine-Needle , Carcinoma, Papillary/diagnosis , Carcinoma, Papillary/genetics , Family Health , Genetic Predisposition to Disease , Thyroid Gland/physiopathology , Thyroid Gland , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/geneticsABSTRACT
Background and purpose: Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating hormone receptor) confers an increased risk of benign thyroid disorders. Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer (NMTC). To explore the hypothesis that polymorphic variation in these genes affects the risk of NMTC. Methods: Tg A7589G and TSHR C253A polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (FCR-RFLP) method, to analyze the relationship between the Tg and TSHR gene polymorphisms and NMTC in NMTC and control groups. Results: Among 360 cases, there was no statistic difference in the frequencies of genotype and allele of TSHR C253A between NMTC and control groups. There were Tg A7589G polymorphisms in the 360 cases. The frequencies ofAG+GG genotype in NMTC group were significantly higher than those in control groups (P<0.05). The frequencies of G allele in NMTC group were significantly higher than those in control groups (P<0.001). Conclusion: There were Tg A7589G gene polymorphisms in NMTC and control groups. G allele may be the predisposing gene of NMTC.