Northern Caribbean University
Patience Bazuaye-Alonge ,Associate Professor at the Biology, Chemistry and Environmental Science Department; Northern Caribbean University Jamaica is a speaker at Gynecology-2014 conference
Background: Cervical cancer which is a preventable disease has impacted tremendously on women’s health in the Caribbean with estimated incidence of 35.8/100,000. In a Jamaican population the role of a polymorphism at position 72 of the tumour suppressor gene p53 in the development of cervical dysplasia and cervical cancer was investigated. This is a population that has high prevalence in HPV associated cervical dysplasia and cervical cancer. Previous studies from other populations have suggested that the arginine variant of the p53 protein could be more susceptible to degradation by human papilloma virus (HPV) E6 protein than the protein containing proline. Many studies however have shown inconsistent and controversial results. P53 genes have been implicated in other cancers such as lungs, neck, and endometrial cancers.
Method: Cases and controls subjects were selected consecutively from women attending colposcopy and genecology clinics respectively. DNA samples from 217 women with cervical dysplasia and cervical cancer and 91 women with normal cervical cytology were analyzed for p53 gene polymorphism. DNA was subjected to restriction enzyme digestion using Sac II and sma I enzymes respectively. The associations between p53 gene polymorphism among cases and controls were explored using logistic regression.
Results and Discussion: The frequency distribution of p53 codon 72 genotypes and the allelic frequencies of the p53 codon 72 arginine and proline allelic variants did not differ significantly in women with cervical dysplasia as a group and normal healthy controls. The results from this population did not support previous studies conducted elsewhere which reported an increased risk of cervical cancer in women homozygous for the p53 codon 72 Arg genotype. But in the Jamaican cohort, there was a statistically significant decrease in the p53 arginine variant in women with CIN III compared to healthy controls (p= 0.037; OR, 0.56, 95% CI 0.34- 0.94) and a statistically significant increase in the p53 proline variant (p = 0.037; OR, 1.78; 95% CI 1.07-2.94). The arginine variant was also significantly decreased in women with high grade squamous intraepithelial lesions (HGSIL) compared to low grade squamous intraepithelial lesion (p = 0.028; OR 0.61, 95%CI 0.40-0.93) and the proline variant increased significantly (p = 0.028, OR, 1.65, 95% CI 1.078 – 2.513). The heterogeneity in the results obtained in different cohorts, including the present study, indicate that the relationship between the p53-codon72 Arg genotype and HPV associated cervical cancer is not a direct one and it may be more complex than was first postulated and might involve additional factors.
Conclusion: the results indicate no relationship between the p53 Arg genotype and susceptibility to cervical dysplasia in Jamaican women; however this genetic variant appears to be negatively associated with cervical cancer. This is the first report of p53 genetic association in Jamaica and further investigations of this relationship is warranted.