title: Association of MDM2 and p53 polymorphisms with the advancement of cervical carcinoma.
abstract: Cervical cancer is one of the most common gynecological malignancies that causes a serious health problem worldwide. The aim of the present study was to analyze the association of p53 codon72 (arginine/proline) polymorphism (rs1042522) and Murine Double Minute 2 (MDM2) SNP309 T/G (rs2279744) with the advancement of cervical cancer by using polymerase chain reaction-restriction fragment length polymorphism method followed by direct sequencing. The frequencies of GG genotype at 309 position in the second promoter (P2) of MDM2 and Arginine in codon72 of p53 were found to be 3.5 (odds ratio [OR]=3.51; 95% confidence interval [CI]=1.93-6.4; p<0.0001) and 5 (OR=4.978; 95% CI=2.7-9.2; p<0.0001) fold higher, respectively, in cases than in the control. On gene-gene interactions between MDM2 and p53 polymorphisms, the frequency of MDM2 G/G and p53 Arg/Arg together was found to be 6.5-fold higher in cervical cancer patients compared with healthy controls (OR=6.497; 95% CI=2.987-14.13; p<0.0001). We found an association of p53 codon72 arginine and MDM2 SNP309 GG genotype with different clinical and histological grades, human papillomavirus (HPV) infection, and age at the time of diagnosis of cervical cancer. In conclusion, Arginine at codon72 of p53 and GG genotype at 309 in P2 of MDM2 together reveal a direct proportionality with the tumor grade of cervical cancer along with HPV infection in postmenopausal women.
authors.affiliation: Divison of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, Noida, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Singhal
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.forename: Nisha
authors.initials: N
authors.lastname: Thakur
authors.forename: Swaraj
authors.initials: S
authors.lastname: Batra
authors.forename: Sudha
authors.initials: S
authors.lastname: Salhan
authors.forename: Suresh
authors.initials: S
authors.lastname: Bhambani
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001120:Arginine / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D055815:Young Adult
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D051736:Proto-Oncogene Proteins c-mdm2