OBJECTIVESTo elucidate the association between genetic polymorphisms ofCYP2a6 andCYP2E1 and urothelial cancer susceptibility.

METHODSA total of 137 Japanese patients with urothelial cancer and 217 Japanese healthy controls, frequency-matched for age and gender, were selected. The polymorphisms ofCYP2A6 andCYP2E1 were analyzed by PCR-RFLP, and cigarette smoking histories were obtained through interviews

RESULTSThe frequency ofCYP2A6 homozygote deletion genotype was 2.9% in the patients, compared with 3.2% in the controls (OR=0.84, 95% CI 0.24-2.96). The frequencies ofCYP2E1 C1/c2 andC2/c2 were 27.7% and 4.4% in the patients, compared with 35.5% and 6.0% in the controls (OR=0.68, 95% CI 0.42-1.09, OR=0.67, 95% CI 0.24-1.84, respectively). No statistically significant differences were observed when theCYP2A6 homozygote deletion genotype and theCYP2E1 genotypes were examined relative to smoking status.

CONCLUSIONSOur data indicate that neither a relationship between genetically impaired nitrosamine metabolism and tobacco-smoking consumption, nor urothelial cancer risk related to theCYP2A6 deletion genotype andCYP2E1 Rsa I genotype was found in Japanese population.

OBJECTIVE: To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. METHODS: The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. RESULTS: The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). CONCLUSION: Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC.
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell* ; Cervix Uteri ; Chemoradiotherapy ; Disease-Free Survival ; Epithelial Cells* ; Female ; Humans ; Multivariate Analysis ; Radiotherapy* ; Retrospective Studies ; Uterine Cervical Neoplasms*

OBJECTIVE: Presence of high-risk factor in cervical cancer is known to be associated with decreased survival outcomes. However, the significance of multiple high-risk factors in early-stage cervical cancer related to survival outcomes, recurrence patterns, and treatment implications is not well elucidated. METHODS: A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n=540). Surgical-pathological risk factors were examined and tumors expressing > or =1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n=177, 32.8%). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy. RESULTS: There were 68 cases (38.4%) expressed multiple high-risk factors (2 high-risk factors: n=58, 32.8%; 3 high-risk factors: n=10, 5.6%). Multiple high-risk factors remained an independent prognosticator for decreased survival outcomes after controlling for age, histology, stage, and treatment type (disease-free survival: hazard ratio [HR], 2.34; p=0.002; overall survival: HR, 2.32; p=0.007). Postoperatively, 101 cases (57.1%) received concurrent chemoradiotherapy (CCRT) and 76 cases (42.9%) received radiotherapy (RT) alone. CCRT was beneficial in single high-risk factor cases: HRs for CCRT over RT alone for cumulative risk of locoregional and distant recurrence, 0.27 (p=0.022) and 0.27 (p=0.005), respectively. However, tumor expressing multiple high-risk factors completely offset the benefit of CCRT over RT alone for the risk of distant recurrence: HR for locoregional and distant recurrence, 0.31 (p=0.071) and 0.99 (p=0.980), respectively. CONCLUSION: Special consideration for the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.
Adult ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Hysterectomy/*methods ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Uterine Cervical Neoplasms/pathology/*surgery