P53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in Uganda

ML Tornesello^a, K Waddell^b, ML Duraturo^a, B Biryahwaho^c, R Downing^c, SB Lucas^d, L Buonaguro^a, FM Buonaguro^a

^aViral Oncology and AIDS Reference Centre, Natl. Cancer Inst. "Fond. Pascale", Naples, Italy, ^bUganda Eye Project, Uganda, ^cUganda Virus Research Institute, Uganda, ^dDepartment of Histopathology, UCL Medical School, London, United Kingdom

Aim: Several studies in the last decade have associated the two polymorphisms at codon 72, arginine and proline, of p53 protein to different types of cancers in different geographical regions. This study aimed to verify the role of p53 polymorphisms at codon 72 in invasive conjunctival squamous cell carcinoma (ICSCC) from Uganda, a sub-Saharan country with one of the highest incidence of ICSCC in the World, characterized by a further 8-fold increase in the AIDS era. Methods: All patients affected by conjunctival neoplastic and pre-neoplastic lesions, along with matched case-control subjects with conjunctival non-neoplastic lesions have been enrolled at out-patient clinics within the Ugandan Eye project. DNA samples were obtained from 41 ICSCC, 33 conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 CIN1-2 and 115 matched controls. p53 codon 72 polymorphism analysis was performed by two independent PCR reactions, based on two sets of oligoprimers specific for Pro (CCC) or Arg (CGC) coding sequence, respectively. Results: The Arg/Arg 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). The increased risk of ICSCC [odds ratio (OR), 5.10; 95% confidence interval (CI), 1.5-17.7] and CIN3 (OR, 4.0; 95% CI, 1.0-15.6) conferred by p53 Arg homozygosity (versus Pro/Pro and Arg/Pro) was not observed in CIN1-2 lesions (OR, 1.2; 95% CI, 0.2-6.9). Moreover, within each analyzed group the frequency of the Arg allele in HIV-positive was not significantly different from that observed in HIV-negative subjects. Conclusions: We conclude that in the Ugandan population p53 Arg/Arg genotype is a key risk factor for invasive squamous cell carcinoma of the conjunctiva and for advanced pre-invasive lesions (CIN3), independently from HIV-related risk factors.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 896 (Tumor suppressor genes).