STK15 polymorphism and breast cancer risk in a population-based study

STK15 is considered a potential cancer susceptibility gene owing to its functions in normal cell mitosis. Two common coding region polymorphisms in the gene (F31I and V57I) may affect ubiquitin-dependent degradation and thus the half-life of the encoded protein. There are limited data on the relevance of these polymorphisms to population cancer rates. To examine whether functional variation in STK15 may affect breast cancer risk, we genotyped a large series of incident breast cancer cases (n = 941) and age-matched population controls (n = 830) for the F31I and V57I polymorphisms. Individually, neither the F31I polymorphism [odds ratio (OR) 1.54; 95% confidence interval (CI) 0.96-2.47, comparing 31I with 31F homozygotes] nor the V57I polymorphism (OR 0.92; 95% CI 0.50-1.71, comparing 57I with 57V homozygotes) was significantly associated with breast cancer risk. A relatively common genotype, combining the two polymorphisms (31I-57V/31I-57V, 3% of controls) was related to a significant 2-fold increase in the risk of post-menopausal breast cancer (OR 1.96; 95% CI 1.01-3.79). No interaction was detected between STK15 variants and estrogenic risk factors, although the power of these analyses was limited. These results suggest that STK15 may represent a low penetrance type breast cancer susceptibility gene.     

Revised rat multi-organ carcinogenesis bioassay for whole-body detection of chemopreventive agents: modifying potential of S-methylcysteine

The DMBDD rat multi-organ carcinogenesis model based on two-stage carcinogenesis theory was revised to make more suitable assay system for detecting chemopreventive effects of chemical substances by increasing the doses of two carcinogens, 1,2-dimethylhydrazine dihydrochloride (DMH) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The revised bioassay resulted in increasing preneoplastic or neoplastic lesions in the colon, urinary bladder and liver. S-Methylcysteine (SMC), a water-soluble organosulfur compound, was used as a test chemical in the new initiation regimen. Though SMC did not express clear-cut inhibitory effects in tumor levels, it showed modifying effects on the development of lung hyperplastic and colon preneoplastic lesions. In conclusion, the present model featuring high yields of preneoplastic and neoplastic lesions with low mortality in a short period (30 weeks), might be suitable for testing the efficacy of possible chemopreventive chemicals at the whole-body level.     

A multi-institutional survey of the effectiveness of chemotherapy combined with radiotherapy for patients with nasopharyngeal carcinoma

BACKGROUND: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved. METHODS: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone. RESULTS: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261). CONCLUSION: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.     

Sentinel lymph node biopsy in oral cancer

Management of the cervical lymph nodes is one of the most important factors in controlling head and neck carcinoma. The clinical treatment strategy for managing the N0 neck in oral cancer is still under debate. Recently, the accuracy and feasibility of sentinel lymph node biopsy (SNB) have been investigated in many studies. An application of the technique to the area of oral cancer was therefore obvious. We reported the technique and accuracy of SNB in our center, and have reviewed the preliminary reports indicating that sentinel node identification is technically feasible in oral and pharynx cancer stages T1 and T2 with clinical N0. However, a multi-institutional trial is needed to determine whether SNB should become a standard procedure.     

A case of liver metastases of breast cancer successfully treated by combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab

A 43-year-old woman underwent breast-conserving therapy for right breast cancer with multiple liver metastases (pT3N3aM1, stage IV, ER (-), PgR (-), HER2 (3+)), in November, 2002. Following surgery, she received combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab weekly. During therapy, no serious side effects and only grade 1 nausea were observed; after 3 courses, therapy was safely continued on an outpatient basis. Metastatic liver tumors responded to the treatment, and they completely disappeared on an abdominal CT 5 months later. In addition, all elevated tumor markers in serum decreased to the normal range. No new metastatic or recurrent lesions were found 14 months after surgery. We conclude that this combination chemotherapy is safe and may be very useful for the treatment of breast cancer patients with liver metastasis.     

Pancreatic Cancer Registry in Japan: 20 years of experience

The prognosis of pancreatic cancer is defined by the histology and extent of disease. Preoperative histologic diagnosis and diagnostic imaging are fundamentals in managing the disease, but it is not rare to find unexpected peritoneal dissemination or liver metastasis at the time of operation. The overall resectability rate of pancreatic cancer is 40% in Japan. Resecting the portal vein and peripancreatic plexus were performed on 40% of the patients who underwent pancreatectomy for invasive cancer in the head of the pancreas. Long-term survival was only found in patients who underwent pancreatectomy. Radical lymph node dissection, or combined resection of the large vessels, did not seem to improve survival further than the standard resection. Multidisciplinary treatments combined with surgery were performed, and various effects of postoperative chemotherapy after pancreatectomy, intraoperative- and postoperative-radiation therapy, or postoperative chemotherapy for unresectable tumor, were shown. Development of unconventional therapies and refinement of the conventional therapy should be promoted on a randomized prospective trial basis. To promote this effort, which requires the international comparisons and cooperation, JPS developed a computerized JPS registration system downloadable from the JPS website (http://www.kojin.or.jp/suizou/index.html).