TP53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in Uganda.
BACKGROUND
The most common TP53 gene polymorphism, which alters the amino acid sequence of the oncosuppressor p53 protein, is located at the codon 72, resulting in either Pro72 or Arg72 p53 variant. Several studies have associated this polymorphism with different types of cancer. We have analyzed the distribution and the role of TP53 Arg72 and Pro72 alleles in conjunctival neoplasia.


METHODS
The study included 41 invasive conjunctival squamous cell carcinoma (ICSCC), 33 conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 of moderate grade (CIN1 and CIN2), and 115 controls from Uganda, a sub-Saharan country with the highest incidence rate of conjunctival neoplasia in the World, particularly in the era of AIDS. The TP53 Arg/Arg codon 72 genotype was detected in 21.9% of ICSCC and in 18.2% of CIN3 but only in 6% of CIN1-2 and in 5.2% of controls (P<0.05).


RESULTS
These data show an increased risk of ICSCC (odds ratio (OR)=6.2, 95% confidence interval (CI): 1.6-24.6) and CIN3 (OR=4.1, 95% CI: 1.0-18.0) associated with TP53 Arg homozygosity, not observed in CIN1-2 lesions (OR=0.8, 95% CI: 0.1-5.1). Moreover, the frequency of the Arg homozygosity was similar in HIV-positive and HIV-negative groups. We conclude that TP53 Arg/Arg codon 72 genotype is a relevant risk factor for invasive squamous cell carcinoma of the conjunctiva and for CIN3 in the Ugandan population.


CONCLUSIONS
The absence of statistically significant difference in the distribution of TP53 Arg72 or Pro72 encoding alleles between HIV-positive and -negative subjects, affected by conjunctival neoplasia, suggests that HIV infection and/or the associated immunodeficiency represent further independent risk factors for ICSCC.
Tornesello
Maria Lina
ML
Viral Oncology and AIDS Reference Centre, National Cancer Institute "Fondazione Pascale", Cappella Cangiani, I-80131 Naples, Italy.
Waddell
Keith M
KM
Duraturo
Maria Luisa
ML
Biryahwaho
Benon
B
Downing
Robert
R
Lucas
Sebastian B
SB
Giani
Umberto
U
Buonaguro
Luigi
L
Buonaguro
Franco M
FM
D000328:Adult; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D003230:Conjunctival Neoplasms / Q000235:genetics* / Q000821:virology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014454:Uganda