p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx.
BACKGROUND
Tobacco smoking, alcohol abuse, and high-risk human papillomavirus (HPV) are risk factors in the etiology of oropharyngeal squamous cell carcinomas (SCCs). The TP53 polymorphism, in which an arginine (R) is changed to proline (P) at codon 72, is functionally significant and could therefore be a predisposing genetic defect.


METHODS
The aim of the study was to investigate the role of codon 72 polymorphism by means of double gradient-denaturing gel electrophoresis in 77 oropharyngeal SCC patients including 33 TP53 mutated and 16 HPV-16-positive cases. The controls consisted of 141 consecutive healthy blood donors.


RESULTS
The cases and controls showed significantly different genotype distribution (P = .0005): the frequencies of the RR, RP, and PP genotypes among the cases were, respectively, 81.8%, 10.4%, and 7.8%, as opposed to 59.6%, 33.3%, and 7.1% among the controls, in agreement with the Hardy-Weinberg equilibrium (P = .35). The PP genotype was significantly overrepresented among females (22.2% vs 3.4%; P = .0243) and in HPV-16-positive cases (25.0% vs 3.3%; P = .0152). No segregation was found between either of the codon 72 genotypes and age or TP53 mutations.


CONCLUSIONS
The significantly lower frequency of the RP genotype in the patients as a whole suggests that it has a protective effect on oropharyngeal SCCs. Moreover, the PP genotype may be a risk factor for the development of oropharyngeal SCC by females and the development of HPV-16-related SCC, although the findings need to be validated in a larger number of tumors.
Perrone
Federica
F
Unit of Experimental Molecular Pathology, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. federica.perrone@istitutotumori.mi.it
Mariani
Luigi
L
Pastore
Elisa
E
Orsenigo
Marta
M
Suardi
Simona
S
Marcomini
Barbara
B
DaRiva
Luca
L
Licitra
Lisa
L
Carbone
Antonino
A
Pierotti
Marco A
MA
Pilotti
Silvana
S
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics*; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53