RESUMEN
A common germline polymorphism of p53 gene produces an Arginine to Proline change at aminoacid position 72. The resulting codon 72 variants have been reported associated with tumor susceptibility since they reduce p53 ability to activate apoptosis. Codon 72 polymorphism may play a role in subside vulnerability to different carcinogens and might account for ethnic variations in cancer frequency. Using an allele-specific polymerase chain reaction (PCR), we tested peripheral blood samples from 98 patients with thyroid cancer, including 21 follicular (FC) and 77 papillary carcinomas (PC), 44 patients with benign nodules, including 14 follicular adenomas and 30 goiters and 153 healthy individuals from the same geographical region. Data on lifetime occupational history, smoking history, general health conditions, previous diseases and other anamnestic data were obtained through interviews. Patients with FC (Pro/Pro = 19.0%, Arg/Arg = 42.9%, Arg/Pro = 38%) and with PC (Pro/Pro = 10.3%, Arg/Arg = 36.36%, Arg/Pro = 53.24%) showed a significant overrepresentation of codon 72 variants compared to the control population (Pro/Pro = 1.9%, Arg/Arg = 33.3%, Arg/Pro = 64.7%) (P = 0.0015). The Pro/Pro genotype, after adjusting for gender, age, tobacco and drugs, was associated with a markedly higher risk of FC (OR=9.714; CI: 2.334-40.436) and of PC (OR=5.299; CI: 2.334-40.436). These results provide evidence that p53 polymorphism is implicated in thyroid carcinogenesis and that individuals harboring the Pro/Pro genotype have an increased risk of developing thyroid cancer.
Asunto(s)
Adenocarcinoma Folicular/genética , Adenoma/genética , Carcinoma Papilar/genética , Genes p53/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Polimorfismo Genético , Enfermedades de la Tiroides/genética , Neoplasias de la Tiroides/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinógenos/efectos adversos , Estudios de Casos y Controles , Codón/genética , Femenino , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prolina/químicaRESUMEN
Screening tools are of utmost necessity in order to identify individuals at risk for thyroid nodule cancer. The polymorphic inheritance of human drug-metabolizing enzymes, such as those encoded by the Glutathione-S-Transferase (GST) system, plays an important role in the development of most human cancers. GSTP1 enzyme is the most important detoxification enzyme in human head and neck tissues. An aminoacid substitution (1105V) in the GSTP1 gene result in two genotypes, GSTP1AB and GSTP1BB. Those produce a variant enzyme with lower activity and less capability of effective detoxification of carcinogens than the wild type GSTP1AA. In order to look for the influence of GSTP1 enzymes inheritance pattern on thyroid cancer risk we used a PCR-SSCP-sequencing approach to compare the genotypes of 98 malignant nodules, including 77 papillary carcinomas (PC) and 21 follicular carcinomas (FC), to 44 benign nodules and to 157 healthy control individuals. Individuals with history of previous thyroid disease, exposure to radiation and antecedents of malignancy were excluded. Patients with PC and FC showed a significant over-representation of the variants of GSTP1 allele compared to the control population (p < 0.0001 The risk for thyroid cancer in individuals with the variant GSTP1 enzymes, after adjusting for gender, age, tobacco and drugs use, increased 7,092 (CI: 2,307-21,802) and 9,625 (CI: 2.484-37.291) times for PC and FC, respectively. We suggest that GST genotype may be associated with an increased susceptibility to thyroid cancer. GSTP1 profiling from peripheral blood may be a simple and useful tool in the screening for thyroid nodule malignancy. Glutathione-S-Transferase system; GSTP; Thyroid cancer; Screening.