A functional T to G germline polymorphism in the promoter region of murine double-minute 2 homolog single nucleotide polymorphism 309 (MDM2-SNP309) has been reported to profoundly accelerate tumor formation, suggesting that it may also represent a powerful cancer predisposing allele. In this study, MDM2-SNP309 was examined in a total of 400 blood samples from 108 normal, 88 cervical, 119 endometrial and 85 ovarian cancer cases using two independent polymerase chain reaction assays for each allele. When the MDM2-SNP309 genotype was classified into two subgroups of TT+TG and GG, the GG genotype was associated with an increased risk for the development of endometrial cancer (odds ratio [OR]= 1.91, 95% confidence interval [CI] = 1.05 to 3.47) compared with the TT+TG genotype (P = 0.0353). The G allele also increased the risk of endometrial cancer (OR = 1.20, 95% CI = 0.83 to 1.74) compared with the T allele, but no statistical difference was found (P = 0.3333). The homozygous GG genotype was also associated with postmenopausal status and type I endometrial cancer (P = 0.0306 and 0.0326, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and cervical or ovarian cancer patients. These results suggest that homozygous GG genotype of MDM2-SNP309 may be a risk factor for postmenopausal and type I endometrial cancer in a Japanese population.

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.

Genetic polymorphisms of p53 and its negative regulator murine double minute 2 homolog (MDM2) have been shown to be closely associated with tumorigenesis in a variety of human cancers. In the present study, single nucleotide polymorphism (SNP) at p53 codon 72 and MDM2 promoter 309 was examined for germline DNA samples from 102 endometrial cancer cases and 95 controls using polymerase chain reaction-based fragment analysis. There were no significant differences in the genotype and allele prevalence between control subjects and endometrial cancer patients for p53 codon 72. The GG genotype frequency of MDM2-SNP309 was statistically higher in endometrial cancer patients than that in normal healthy women when compared with the TG genotype (P= 0.0088). However, no statistically significant differences were found between the TT and TG or GG genotype frequencies and allele prevalence. Interestingly, the combination of the homozygous Arg/Arg genotype of p53 codon 72 and homozygous GG genotype of MDM2 SNP309 polymorphisms was significantly associated with the risk of endometrial cancer (odds ratio = 3.28, 95% confidence interval = 1.13 to 9.53, P= 0.0212). The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population.

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To clarify the issues associated with the applications of virtual microscopy to the daily cytology slide screening, we conducted a survey at a slide conference of cytology. The survey was conducted specifically to the Japanese cytology technologists who use microscopes on a routine basis. Virtual slides (VS) were prepared from cytology slides using NanoZoomer (Hamamatsu Photonics, Japan), which is capable of adjusting focus on any part of the slide. A total of ten layers were scanned from the same slides, with 2 micrometer intervals. To simulate the cytology slide screening, no marker points were created. The total data volume of six slides was approximately 25 Giga Bytes. The slides were stored on the Windows 2003 Server, and were made accessible on the web to the cytology technologists. Most cytotechnologists answered "Satisfied" or "Acceptable" to the VS resolution and drawing speed, and "Dissatisfied" to the operation speed. To the ten layered focus, an answer "insufficient" was slightly more frequent than the answer "sufficient", while no one answered "fewer is acceptable" or "no need for depth". As for the use of cytology slide screening, answers "usable, but requires effort" and "not usable" were about equal in number. In a Japanese cytology meeting, a unique VS system has been used in slide conferences with markings to the discussion point for years. Therefore, Japanese cytotechnologists are relatively well accustomed to the use of VS, and the survey results showed that they regarded VS more positively than we expected. Currently, VS has the acceptable resolution and drawing speed even on the web. Most cytotechnologists regard the focusing capability crucial for cytology slide screening, but the consequential enlargement of data size, longer scanning time, and slower drawing speed are the issues that are yet to be resolved.