Is there a survival benefit to adjuvant radiotherapy in high-risk surgical stage I endometrial cancer?

OBJECTIVE: The aim of this study was to examine the effects of therapeutic modalities on survival of stage I endometrial cancer and also to evaluate the surgical morbidity and the prognostic importance of surgicopathological variables. METHODS: A hundred and ninety-six stage I endometrial cancer patients treated at Hacettepe University Hospital between 1982 and 1997 were included. After initial diagnosis all patients underwent surgical procedures including peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salphingoopherectomy, and complete pelvic-paraaortic lymphadenectomy. The mean age at initial diagnosis was 56 years (SD = 9.9 years) and the patients were followed 3-18 years (median, 8 years). All patients had endometrioid carcinoma. Stage IC and/or grade 3 tumors were considered high-risk factors and by this definition 147 (75%) patients were low risk and 49 (25%) patients were high risk. Forty-nine percent of high-risk patients received adjuvant radiotherapy compared with 3.5% of patients in the low-risk group. RESULTS: The 10-year disease-free and overall survival rates of the entire group were 97 and 98%, respectively. Ten-year overall survival rate for the low-risk group was 100% compared with 94% for patients with high-risk features (P = 0.002). The 10-year disease-free survival rate in the high-risk group was 96% for 24 patients who received adjuvant radiotherapy versus 92% for 25 patients who did not receive adjuvant therapy (P = 0.53). Only high grade was a significant predictor of poor survival (P = 0.0004). Overall surgical morbidity rate was 8.1% without mortality related to surgery. CONCLUSIONS: Surgical staging achieved excellent survival for stage I endometrial cancer patients without incurring untoward morbidity and mortality. No survival advantage of adjuvant radiotherapy was detected even for high-risk patients, so we suggest the use of radiotherapy may be reserved for relapse.

CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.

OBJECTIVE: Gene-environment interactions have been the focus of a number of recent studies of the occurrence of human cancers, and an association between the risk and the CYP1A1*3 polymorphism has been noticed for several cancers. Previous studies suggest that estrogens are involved in the etiology of ovarian cancer. The cytochrome P450 1A1 (CYP1A1) gene polymorphism may play role in the development of epithelial ovarian neoplasm by detoxification of polycyclic hydrocarbons and other compounds and the concentration of estrogens and their metabolites. Therefore, we assessed the association of CYP1A1 gene polymorphism in patients with epithelial ovarian neoplasm in the Turkish populations through a case-control study. METHODS: Using an allele-specific polymerase chain reaction (PCR)-based method, CYP1A1*3 polymorphism, in exon 7 of the gene, was analyzed in 117 epithelial ovarian neoplasm patients and 202 control subjects. RESULTS: The CYP1A1 Ile/Val genotype significantly increased the risk for patients with epithelial ovarian neoplasm (OR 5.7, 95% CI 3.34-9.76). Furthermore, there were statistical differences in the distribution of CYP1A1 Val/Val genotype among all patients (OR 5.85, 95% CI 2.40-14.25). In other words, the presence of the Val allele significantly increased the risk of epithelial ovarian neoplasm. Among benign tumors, the frequency of Ile/Val and Val/Val genotypes was found to be statistically significant with an ORs of 6.01 and 4.38 (95% CI 2.61-13.84 and 1.04-18.38, respectively). In the benign serous ovarian tumors, patients with Ile/Val and Val/Val revealed a 7.2- and 10.5-fold higher risk of having ovarian carcinoma (95% CI 2.22-23.40 and 2.16-51.19), respectively. In the benign mucinous ovarian carcinoma patients, the frequency of Ile/Val was found to be statistically significant with an OR of 5.15 (95% CI 1.75-15.16). However, no patient with Val/Val genotype was observed in this group and no statistical distribution was performed. Among borderline tumors, CYP1A1 Ile/Val genotype significantly increased the risk for patients (OR 5.15, 95% CI 1.75-15.16). However, only one patient was observed with the Val/Val allele and the frequency of this genotype was not found to be statistically different with an OR of 2.50 (95% CI 0.27-22.64). Among ovarian cancer patients, there were statistically differences in the distribution of CYP1A1 Ile/Val and Val/Val genotypes (OR 5.73, 95% CI 3.04-10.76; and OR 7.42, 95% CI 2.80-19.66), suggesting that patients carrying these genotypes were at increased risk for ovarian carcinoma. In serous carcinoma, patients with CYP1A1 Ile/Val and Val/Val revealed a 6.5- and 10-fold higher risk of having ovarian cancer (OR 7.09, 95% CI 3.30-15.22; and OR 8.77, 95% CI 2.83-27.14). In mucinous carcinoma, patients with CYP1A1 Ile/Val and Val/Val also revealed a 5.4 and 10.5 times higher risk of having ovarian cancer. There were no statistical significance in the distribution of Val allele among endometroid-type cancer patients. CONCLUSIONS: Our data, although based on a small number of subjects, suggest that variant alleles of CYP1A1 gene in ovarian epithelial cells, directly or through other components, may contribute to initiation of ovarian carcinogenesis.