Anticipación genética en el carcinoma papilar familiar de tiroides
- Camacho Luna, Amaro José
- Antonio Ríos Zambudio Director
- José Manuel Rodríguez González Director
- Manuel Durán Poveda Director
Defence university: Universidad de Murcia
Fecha de defensa: 20 July 2023
- Francisco Sánchez-Bueno Chair
- José Ruiz Pardo Secretary
- Pedro Cascales Sánchez Committee member
Type: Thesis
Abstract
Introduction- Genetic anticipation is a concept with a controversial history which is difficult to quantify, and which has a poorly defined study systematics. This phenomenon is observed in hereditary diseases in which individuals exhibit an increasingly aggressive clinical picture and earlier manifestation of clinical signs over successive generations. This phenomenon has a proven genetic basis and has been solidly associated with several different diseases such as myotonic dystrophy or Huntington’s disease. Since 2008, some studies have tried to find an association between familial papillary thyroid carcinoma and the genetic anticipation phenomenon, with both negative and positive results being reported by different studies. However, the sample size, the origin of the study subjects and the methodology of these studies generate a low evidence level in this topic. The goal of the present study is to investigate the existence of genetic anticipation by analyzing and comparing the age at diagnosis, variables associated with histological malignant behavior, the prognostic staging at the time of diagnosis and the evolution of the disease between different generations, through healing and recurrence rates. Materials and methods- We present a longitudinal, multi-institutional analytical study within the spanish territory, endorsed by the Spanish Association of Surgeons, and developed between 2015 and 2018. One hundred and thirty patients from 47 families with at least two members diagnosed with familial papillary thyroid carcinoma were studied. The patients were divided in first generation and second or successive generation groups and both groups were compared. Variables analyzed included age, factors associated with histological malignant behavior, prognostic staging at the time of diagnosis and follow-up variables (healing and recurrence rates). Results- The second generation group was diagnosed at a younger age, with a mean age of 36 ± 9.5 years old compared to 53 ± 11 years old for the first generation. 96.2% of the second generation group was diagnosed before 55 years old compared to 58% of the first generation group. Histologically, no differences were found between groups other than tumor size, with an average measurement of 23 ± 13mm for the first generation and 13 ± 10mm for the second generation (p<0.001). The first generation showed a more advanced T stage at the time of diagnosis (30% T2 and 30% T3) compared to the second generation (38’7% T1a and 25% T1b) (p-0.014). The first generation group also exhibited a more advanced TNM stage at the time of diagnosis: 52% of the patients were classified as stage I compared to 88.7% of the patients of the second generation classified as this stage (p<0.001). No differences were observed for the N or M staging between groups. No differences were found in the follow-up variables (healing and recurrence rates). Conclusions- In the present study, familial papillary thyroid carcinoma presented at an earlier age in second and successive generations compared to the first generation in which the disease is diagnosed. Additionally, this tumor exhibited a more advanced T as well as TNM stage in the second and successive generations compared to the first affected generation. No histological differences were observed other than tumor size, which was smaller in the second and successive generations compared to the first generation. No differences were observed in the evolution of the disease between groups. The phenomenon of genetic anticipation occurs in familial papillary thyroid carcinoma, with second and successive generations developing the disease earlier in life, the tumor reaching a smaller size, and behaving similarly in aggressiveness and evolution compared to the first generation, therefore losing the protecting factor of age, which is present in sporadic papillary thyroid carcinoma