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Though many investigators have reported relationships between the CCND1 polymorphism and susceptibility to various carcinomas, to our knowledge, no report has been issued concerning its relationship with uterine cervical cancer. Thus, we undertook this study to investigate the association between CCND1 polymorphisms and susceptibility to cervical cancer in Korean women. This study was carried on 222 patients with squamous cell carcinoma of uterine cervix and on 314 normal controls. CCND1 genotyping was determined by polymerase chain reaction and restriction fragment length polymorphism. The allelic frequencies of the cases (A, 0.53; G, 0.47) were not significantly different from those of the controls (A, 0.49; G, 0.51) (P=0.238). Regression analysis after adjusting for age showed that the CCND1 G870A genotypes are not related to the risk of squamous cell carcinoma of the uterine cervix. Our findings suggest that the CCND1 polymorphism is not associated with an increased risk of squamous cell carcinoma of uterine cervix in Korean women.

The aim of this investigation was to analyze the association between a single nucleotide polymorphism (SNP) in the matrix metalloproteinase (MMP)-1 promoter gene -1607 bp region and cervical cancer risk in Korean women. The blood samples of 232 cervical cancer patients and 332 non-cancer control subjects who managed at Seoul National University Hospital from 1999 to 2002 were collected. Polymorphism in MMP-1 promoter -1607 region was determined using TaqMan method. Allele frequency and genotype distribution in the cervical cancer group were compared with those of the control group to determine whether this polymorphism elevates the susceptibility of Korean women to cervical cancer. The relationship between this SNP and cancer invasiveness was also evaluated by collating clinicopathologic data of those in the cancer group, such as FIGO stage, lymph node status, histologic type and parametrial invasion. In the cervical cancer group, the allele frequency of 2G was 66.1%, in the control group 68.2%, showing no significant difference (P=0.41). Similarly the genotypes with insertion (2G/2G) or deletion (1G/1G) polymorphism showed no increased risk for cervical cancer susceptibility compared with 1G/2G genotype. A subgroup analysis of the clinicopathologic parameters in cancer group also showed no significant difference suggesting the lack of an association between SNP of the MMP-1 promoter -1607 bp region and cervical cancer invasiveness. In conclusion, this study shows that Korean with specific polymorphism in MMP-1 are neither more susceptible to develop cervical cancer nor more vulnerable for cancer progression.

Cyclooxygenase-2 (COX-2) expression is mediated by constitutive nuclear factor (NF)-kappaB. The aim of this study was to investigate the association between the germline alteration of the NF-kappaB binding site of COX-2 and the risk of developing various types of human cancers. Using PCR and DNA sequence analysis, we performed a hospital-based case-control study involving various types of human cancers, namely cervical, breast, lung, and bladder cancer. The COX-2 gene was sequenced in 217 Korean individuals (122 cancer patients; 95 non-cancer patients). We identified 2 novel polymorphisms -1166 C-->G and -1186 T-->G, in the NF-kappaB binding promoter region of COX-2. A polymorphism in nucleotide 1186 was found to be associated with an increased risk of bladder cancer (P=0.038). However, in the case of the other cancers, no significant association was found between polymorphisms in the COX-2 promoter region and the risk of cancer. In conclusion, our results suggest that polymorphisms in nucleotide -1186, which is in the NF-kappaB binding promoter region of the COX-2 gene, may be associated with an increased risk of bladder cancer. Further research is needed to investigate the functional implications of the polymorphisms of the COX-2 promoter gene in human cancer.

This study determined the distribution of high-risk HPV type infection in cervical cancer using newly developed oligonucleotide chips (HPVDNAChips). The study subjects included 80 cases of cervical neoplasia and 746 controls with a normal Pap smear. For HPV genotyping, the commercially available HPVDNAChips was used. The risk of cervical cancer was increased in women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92-6.17) and in smokers (adjusted OR=3.2, 95% CI: 1.45-7.06). There was also a trend of increased risk with the number of full term pregnancies (P(for trend)

The aim of this study was to estimate whether the Ile184Arg polymorphism of the Interferon, alpha 17 (IFNA17) gene might be correlated with the risk and prognosis of cervical squamous cell carcinoma (SCCA). Genomic DNA from 173 patients with invasive cervical SCCA and from 198 non-cancer controls (NCC) was examined for the Ile184Arg polymorphism with a polymerase chain reaction-restriction fragment length polymorphism-based assay. All P values are from two-sided tests. The distribution of IFNA17 Ile184Arg genotype among SCCA cases (Ile/Ile, 21%; Arg/Ile, 57%; and Arg/Arg, 22%) was different significantly from that among NCC (Ile/Ile, 32%; Arg/Ile, 56%; and Arg/Arg, 12%) (P=0.0345). A significant increase in 184Ile homozygote frequency was found in the SCCA patients compared with the NCC group (odds ratio 2.96; 95% confidence interval 1.53–5.73; P=0.001). However, differences in clinicopathologic prognostic factors and in the 5 year survival rate were not significant among the subjects of each genotype group (P>0.05). The results of this study suggest that the 184Ile homozygote of the IFNA17 gene may represent an important susceptibility biomarker for cervical cancer risk.

We utilized three cervical cancer cell lines (HeLa, HT-3, and C33A) and clonogenic assays to determine whether cyclooxygenase (COX) expression is related to radiosensitivity. Using COX DNA transfection and COX inhibition by siRNA, we also examined changes in radiosensitivity caused by variations in COX expression. The survival fractions of HeLa and HT-3 cell lines, which both with COX-1 and COX-2 activity, were found to be significantly higher than that of the C33A cell line which had neither COX-1 nor COX-2 activity. Moreover, the acquisition of COX-1 in C33A cell line significantly reduced its radiosensitivity, but COX-2 transfection increased radiosensitivity in this cell line. In addition, the inhibition of COX-1 activity in HT-3 cell line using siRNA resulted in an increased radiosensitivity, but this phenomenon was not observed for COX-2 inhibition. The same experiment in HeLa cells using siRNA also showed no significant change in radiosensitivity. The results obtained during this study suggest that COX expression is associated with the radiosensitivity in uterine cervical cancer cell lines and COX-1 might have more important role than COX-2.

The evaluation of expression levels of the estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer is a very common procedure in modern practice. However, the significance of such tests remains controversial, and the evaluation of the status of steroid receptors seems to be a more thoroughly justified practice. The present study was carried out with 145 endometrial cancer patients, all of whom had undergone operations at the Seoul National University Hospital, from 1993 to 2002. Paraffin-embedded tissue blocks were sectioned and immunostained with monoclonal anti-ER and anti-PR antibodies. Clinicopathological variables were also analyzed, with 10% cutoff values for ER and PR positivity. A multivariate Cox regression analysis was performed in order to estimate the influences of several clinicopathological and immunohistochemical covariates on patient survival. Forty seven specimens (32.4%) stained as ER positive, and 110 (75.9%) stained as PR-positive. Patients with PR-positive tumor tended to be both younger and more obese than patients with PR-negative tumors (P=0.020, 0.016). Well-differentiated tumors were found to be positive for ER or PR more frequently (P=0.015

In a previous study, we demonstrated that elevation of COX-2 is significantly associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix. The main objective of this study is to characterize the relationship between elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84 patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)]. Elevation of COX-2 was correlated with clinicopathological variables and p53 expression, as detected by immunohistochemistry. Elevation of COX-2 was detected in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor stage and lymph node metastasis were correlated with elevation of COX-2 with a borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was not associated with elevation of COX-2. The association between lymph node metastasis and elevation of COX-2 was stronger in cases of AC than in cases of ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis, elevation of COX-2 was significantly associated with decreased overall survival (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor stage was independently associated with overall survival, suggesting that elevation of COX-2 itself may not be an independent prognostic factor. The present study shows that elevation of COX-2 may contribute to lymph node metastasis in AC of uterine cervix. This suggests that the potential therapeutic role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of uterine cervix.

The aims of this study were to determine whether polymorphisms of the interleukin (IL)-10 promoter might be associated with an increased risk of cervical cancer, and further whether systemic IL-10 concentration might be influenced by the genotypes in Korean women. Peripheral blood samples from patients with invasive cervical cancer (ICC, n =144) and non-cancer controls (NCC, n =179) were used to detect three biallelic IL-10 promoter polymorphisms at −1082, −819, and −592 sites by polymerase chain reaction-restriction fragment length polymorphism assay using Mnl I, Mae III and Rsa I, respectively. The IL-10 serum concentration was measured with enzyme-linked immunosorbent assay. We compared the distribution of genotypes in both groups, evaluated the serum IL-10 level according to the genotypes, and analyzed the association of these polymorphisms with the risk of cervical cancer. The genotype at the −1082 site exhibited only the *A homozygote, and only two haplotypes were found in Korean women, one being −1082*A/−819*T/−592*A (ATA) and the other −1082*A/−819*C/−592*C (ACC). No association was found for IL-10 promoter polymorphisms among the ICC patients in comparison with the NCC subjects. The risk of cervical cancer was not increased in either genotype and the IL-10 serum concentration was not influenced by the genotypes in either group. Polymorphisms of the IL-10 promoter do not appear to be associated with cervical cancer risk or systemic IL-10 production in Korean women.

The aim of this study was to determine whether the codon 31 genotype of p21 might be associated with an increased risk of cervical cancer development in Korean women. We used tissue derived from patients with invasive cervical cancer (ICC) (n=111, composed of two histologic groups: squamous cell carcinoma (n=67) and adenocarcinoma (n=44)), cervical intraepithelial neoplasia (CIN) III (n=101), and non-cancer controls (NCC, n=98). For the determination of p21 polymorphism, genomic DNA was examined by polymerase chain reaction–restriction fragment length polymorphism assay using BsmAI. We compared the distribution of the p21 genotype in ICC, CIN III, and control and also analyzed the association of this polymorphism with the risk of development of cervical cancer, especially in patients with high-risk human papillomavirus (HPV) (16 or 18)-positive cervical cancer. A significant increase of Ser/Ser genotype frequency was found in adenocarcinoma patients with high-risk HPV (16 or 18) compared with the NCC group (P=0.009). The odds ratio was 3.59 (95% CI 1.55–8.31) when comparing adenocarcinoma patients associated with high-risk HPV with NCC. We found that the codon 31 Ser/Ser homozygote of the p21 gene could be a risk factor for the development of cervical adenocarcinoma associated with high-risk HPV.