The Association Of P53 Codon 72 And PIN3 Polymorphism With Susceptibility To Ovarian Cancer In Northern Chinese Han Population

Objective: Biological, chemical and physical carcinogens areconsidered as some of the main risk factors for developingcancer. However, not all individuals exposed to the aboveexogenous risk factors will develop caner, indicating that thehost susceptibility factors may play an important role in thecancer development. P53 plays a central role in the processes ofDNA repair and apoptosis. There are three polymorphic sitesthat play a role in carcinogenesis encompassing the 16 bpduplication polymorphism in intron 3(PIN3), the BstU Irestriction fragment length polymorphism(RFLP) at codon 72 inexon 4, and the MspⅠ RFLP in intro 6. These had beeninvestigated to be correlated with some kinds of cancers, such aslung, cervical, esophageal cancer et al. Ovarian cancerrepresents a major cause of cancer death among women and yetremarkably little is known about its etiology. P53 gene isfrequently muted in ovarian cancer. We hypothesized thatpredisposition to ovarian cancer and the clinical course ofdisease may be influenced by epigenetic environmental factorsinteracting through a common intermediate risk polymorphismof the p53 gene. P53 PIN3 has been reported to be in strong 5英 文 摘 要linkage disequilibrium (>0%) with a polymorphism in intro 6,but not with that in codon 72, so we select p53 codon 72 RFLPand PIN3 as our research sites. In this study we investigate theabove two p53 DNA polymorphisms in a hospital based case-control study to determine whether the p53 gene polymorphismplays a part in genetic susceptibility to ovarian cancer. In orderto control for potential regional differences in allelotypeexpression, we have tested our hypothesis on a cohort of ovariancancer patients and controls from northern Chinese Hanpopulation. Methods: 124 patients with epithelial ovarian cancer wererecruited from the gynecology and obstetrics department of theFourth Affiliated Hospital of Hebei Medical University fromDecember 2001 to November 2003. All the epithelial ovariancancer patients were histologically confirmed. Ovarian cancerstaging was performed by FIGO clinical standard. 128 healthyvolunteers who had no clinical evidence of ovarian cancer orany other malignant tumours were randomly selected fromChinese blood donors as control subjects. The information ofage, pregnancy, parity and age of menarche were obtained fromcancer patients and healthy controls by questionary. All casesand controls were from northern Chinese Han population. Theinformed consent was got from all the recruited subjects. . Fiveml of venous blood from each subject was drawn in Vacutainertubes containing EDTA and stored at 4℃. The genomic DANwas extracted within one week after bleeding by using 6英 文 摘 要proteinase K digestion followed by a salting out procedure. Forthe determination of the polymorphism at codon 72 of the p53gene, an allele-specific PCR assay was used to selectively detecteither the Arg or Pro p53 allele. PCR assay was also used todetermine the genotype of PIN3. Statistical analysis wasperformed using the SPSS10.0 software package. Thecomparison of p53 genotype distribution in the study groupswas performed by means of two-sided contingency tables usingChi-square tests. A probability level of 5% was considered asstatistically significant. Results: (1) The general information in ovarian cancerpatients was comparable to the healthy controls. (2) All thegenotype frequencies of both p53 codon72 Arg/Pro and PIN3did not deviate from the expected Hardy-Weinberg distribution.(3) There was no statistical difference in allele distributionbetween ovarian cancer patients and controls both for p53codon72 and PIN3 (P>0.05). The overall p53 codon72 Arg/Proand PIN3 genotype distribution in ovarian cancer patients wasnot significantly different from that among healthy controls(P>0.05). (4) When the epithelial ovarian cancer patients weregrouped ac...