Md Shaki Mostaid

TP53 genetic polymorphisms and susceptibility to cervical cancer in Bangladeshi women: a case–control study

Pharmacogenetic study of TP53 gene polymorphisms has not been conducted extensively in cervical cancer. The aim of this study was to assesses the TP53 codon 72 and codon 47 polymorphisms and their relation to cervical cancer risk in Bangladeshi women. 134 cervical cancer patients and 102 age matched healthy controls were included from two institutions in Bangladesh. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two TP53 single nucleotide polymorphisms (codon 72 and codon 47) in patients and controls. The results indicate that the TP53 Arg/Pro heterozygosity (adjusted OR   2.32, 95% CI  1.28-4.34, p = 0.01), Pro/Pro mutant homozygosity (adjusted OR  4.15, 95% CI  1.75-9.86, p = 0.001), along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR  2.83, 95% CI  1.61-4.97, p < 0.001) significantly increases the risk of cervical cancer. Moreover, the cervical cancer patients with a first-degree relative cancer patient possesses 4.45 folds more risk (p = 0.019) of carrying a proline allele in codon 72 of the TP53 gene compared to those patients who do not have any first-degree relative with cancer. Finally, polymorphism in the codon 47 of the TP53 gene did not significantly increase the risk of cervical cancer in Bangladeshi women. To conclude, this is the first study to identify that polymorphism in the TP53 codon 72 significantly increases the risk of cervical cancer in a female population in Bangladesh.

Elevated serum expression of p53 and association of TP53 codon 72 polymorphisms with risk of cervical cancer in Bangladeshi women

Differential expression of p53 has been reported in cervical cancer, primarily in tumor tissue biopsies. In this study, we examined the association of TP53 codon 47 and codon 72 polymorphisms and serum level expression of p53 in cervical cancer patients (n = 129) and healthy controls (n = 122). We found elevated levels of serum p53 protein levels in cervical cancer patients (p = 0.0442) compared to healthy controls. Moreover, we found higher levels of serum p53 in patients with grade-III tumor (p = 0.001) compared to healthy controls. Examination of SNPs showed TP53 Arg/Pro heterozygosity (adjusted OR = 2.126, 95% CI = 1.181–3.827, p = 0.012), Pro/Pro mutant homozygosity (adjusted OR = 3.564, 95% CI = 1.647–7.713, p = 0.001), along with the combined genotype (Arg/Pro+Pro/Pro) (adjusted OR 2.542, 95% CI = 1.517–4.260, p&lt;0.001) significantly increases the risk of cervical cancer. Expression quantitative trait analysis revealed no significant association with protein expression. Our results represent for the first time the upregulation of serum p53 in cervical cancer in Bangladeshi women and supports the association of TP53 codon 72 polymorphisms with cervical cancer.