Proline homozygosity in codon 72 of p53 is a factor of susceptibility for thyroid cancer.
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.
Granja
Fabiana
F
Laboratory of Cancer Molecular Genetics, Department of Medicine, State University of Campinas, Olympio Pattaro 45, Campinas, São Paulo, Brazil.
Morari
Joseane
J
Morari
Elaine C
EC
Correa
Luiz A C
LA
Assumpção
Lígia V M
LV
Ward
Laura S
LS
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002273:Carcinogens / Q000009:adverse effects; D002291:Carcinoma, Papillary / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline / Q000737:chemistry; D013959:Thyroid Diseases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
D002273:Carcinogens; D003062:Codon; D011392:Proline