Divison of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, Noida, India.
DNA Cell Biol. 2013 Jan;32(1):19-27. doi: 10.1089/dna.2012.1718. Epub 2012 Dec 4.
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.
宫颈癌是全球最常见的妇科恶性肿瘤之一，对健康造成严重威胁。本研究旨在通过聚合酶链反应-限制性片段长度多态性方法结合直接测序，分析 p53 密码子 72（精氨酸/脯氨酸）多态性（rs1042522）和 Murine Double Minute 2（MDM2）SNP309 T/G（rs2279744）与宫颈癌进展的相关性。研究发现，MDM2 第二启动子（P2）309 位 GG 基因型和 p53 密码子 72 位精氨酸的频率在病例组中分别为 3.5（比值比[OR]=3.51；95%置信区间[CI]=1.93-6.4；p<0.0001）和 5（OR=4.978；95% CI=2.7-9.2；p<0.0001）倍高于对照组。在 MDM2 和 p53 多态性之间的基因-基因相互作用中，与健康对照组相比，宫颈癌患者 MDM2 G/G 和 p53 Arg/Arg 同时发生的频率更高，为 6.5 倍（OR=6.497；95% CI=2.987-14.13；p<0.0001）。我们发现 p53 密码子 72 位精氨酸和 MDM2 SNP309 GG 基因型与不同的临床和组织学分级、人乳头瘤病毒（HPV）感染以及宫颈癌诊断时的年龄有关。总之，p53 密码子 72 位精氨酸和 MDM2 P2 位 309 位 GG 基因型与 HPV 感染的宫颈癌肿瘤分级呈正相关，尤其是在绝经后妇女中。
