Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Context: Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one-to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion. Objective: Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD. Subjects and methods: USP8 mutations as well as clinicopathological characteristics were examined in 60 corticotroph adenomas including 15 Crooke's cell adenomas (CCAs), a rare histological variant presenting with generally aggressive behavior, using qRT-PCR and/or immunohistochemistry. Results: USP8 mutations were exclusively detected in women, except for one case, with a prevalence of 42.2% in non-CCA and 13.3% in CCA (overall 35%). Clinically well-behaved presentations including microadenoma and curative resection were more common in mutated cases. The expression of EGFR was not associated with the mutation status. In contrast, mutated tumors expressed significantly higher levels of POMC, SSTR5, and MGMT. Conclusions: Microadenomas that strongly express POMC were common among mutated tumors, which may lead to the mechanisms by which very small adenomas secrete excess ACTH to present overt CD. While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR-mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5. In contrast, non-mutated aggressive tumors such as CCA may respond better to the alkylating agent temozolomide because of their significantly weak expression of MGMT.

Clinically nonfunctioning pituitary adenomas (NFAs) may be hormonally inactive tumors of differentiated cells, mainly not only gonadotroph adenomas (GAs) but also silent corticotroph adenomas (SCAs) and other differentiated silent adenomas. Recently, the use of transcription factors has been recommended to confirm cytodiffererentiation of these neoplasms. Our objective was to assess the clinical significance of the new classification system using transcription factors. Five hundred sixteen consecutive NFAs were studied retrospectively. They were initially classified based on hormone immunohistochemistry as follows: 119 hormone-negative adenomas (23.1 %), 300 GAs (58.1 %), 51 SCAs (9.9 %), and 46 other silent adenomas. The 119 hormone-negative adenomas were further evaluated for expression of transcription factors including steroidogenic factor-1 (SF-1), estrogen receptor-α (ERα), pituitary-specific transcription factor 1 (Pit-1), and t-box transcription factor (Tpit). One hundred thirteen of 119 (95 %) hormone-negative adenomas showed mutually exclusive lineage-specific differentiation as gonadotrophs (SF-1 positive), corticotrophs (Tpit positive), or somatotrophs/mammosomatotrophs/lactotrophs/thyrotrophs (Pit-1 positive) in 79 cases (66.4 %), 32 cases (26.9 %), and 2 cases, respectively. The 32 ACTH-negative and Tpit-positive adenomas had higher pro-opiomelanocortin mRNA expression levels compared with GAs (P = 0.0001) on quantitative real-time PCR. They showed a female preponderance (P < 0.0001) and were more frequently giant adenomas (P = 0.0028) associated with marked cavernous sinus invasion (P < 0.0001) compared with GAs. These clinical features were identical to those of the 51 ACTH-positive SCAs. Our results justify the complementary role of transcription factors in the precise classification of NFAs that can more accurately characterize biological behavior. Our data suggest that more than one quarter of hormone-negative adenomas are SCAs that share distinct clinicopathological features with ACTH-expressing SCAs.

No abstract

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988-90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at -80°C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of ≤ ≤ ≤ ≤10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR = = = =0.39, 95% CI; 0.13, 0.89, trend P = = = =0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose-dependently reduce prostate cancer risk. (Cancer Sci 2004; 95: 65-71) ncidence and mortality rates of prostate cancer are much lower among Japanese men compared with Western populations.1) The incidence of prostate cancer in Japan ranges from around one-twentieth that of African-Americans to one-third that of some European populations, and the disparity in mortality is around one-ninth to one-third, respectively. Many other Asian countries also have lower incidences than Western countries. 2)Phytoestrogens, plant-origin isoflavonoids and lignans with estrogen-like activities, have been identified as key compounds that may decrease the risk of prostate cancer in Asian countries because Asian people consume more phytoestrogen-rich foods such as soybeans than Western people.3, 4) The potential protective effect has been examined by epidemiological studies on the association of prostate cancer risk with isoflavonoid-rich diet or intake of isoflavonoids estimated from nutrient databases, and most of the studies support the effect, as summarized in a review.4) However, very few epidemiological studies have measured serum or urine phytoestrogens directly. A Nordic nested case-control study failed to show any protective effect of circulating enterolactone, a metabolite of lignans.5) A case-control study in Japan showed mostly unexpected results. 6)Epidemiologic data concerning blood levels of androgens are inconclusive, 7) although a recent meta-analysis showed that a high level of total testosterone and low level of sex hormonebinding globulin (SHBG) increased the risk of...

BACKGROUND: The incidence of kidney cancer is high in Western and Northern Europe and North America, and low in Asia. Although the incidence of kidney cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. METHODS: We evaluated the risk factors for kidney cancer death using the database of the Japan Collaborative Cohort (JACC) Study (i.e., medical history, anthropometry, and lifestyle including dietary habits). The analytic cohort included 47,997 males and 66,520 females aged 40 years and older. The Cox proportional hazards model was used to determine adjusted relative risks. RESULTS: A total of 36 males and 12 females died from kidney cancer during the follow-up of 9.6 ± 2.6 years and 9.9 ± 2.2 years, respectively. A medical history of hypertension, a fondness for fatty food, and consumption of black tea were associated with an increased risk of kidney cancer death while an intake of taro, sweet potato and potato was associated with a decreased risk. CONCLUSIONS: The present study showed four factors to be related to kidney cancer death. However, further studies may be needed to evaluate risk factors for kidney cancer death in Japan because the number of kidney cancer death in the present study was small.

No abstract

Background: Gastroesophageal reflux (GER) is common in anesthetized dogs and can cause esophagitis, esophageal stricture, and aspiration pneumonia.Objective: To determine whether preanesthetic IV administration of esomeprazole alone or esomeprazole and cisapride increases esophageal pH and decreases the frequency of GER in anesthetized dogs using combined multichannel impedance and pH monitoring.Animals: Sixty-one healthy dogs undergoing elective orthopedic surgery procedures. Methods: Prospective, randomized, placebo-controlled study. Dogs were randomized to receive IV saline (0.9% NaCl), esomeprazole (1 mg/kg) alone, or a combination of esomeprazole (1 mg/kg) and cisapride (1 mg/kg) 12-18 hours and 1-1.5 hours before anesthetic induction. An esophageal pH/impedance probe was utilized to measure esophageal pH and detect GER.Results: Eight of 21 dogs in the placebo group (38.1%), 8 of 22 dogs in the esomeprazole group (36%), and 2 of 18 dogs in the combined esomeprazole and cisapride group (11%) had 1 episode of GER on impedance testing during anesthesia (P < .05). Esomeprazole was associated with a significant increase in gastric and esophageal pH (P = .001), but the drug did not significantly decrease the frequency of GER (P = .955). Concurrent administration of cisapride was associated with a significant decrease in the number of reflux events (RE) compared to the placebo and esomeprazole groups (P < .05).Conclusions and Clinical Relevance: Preanesthetic administration of cisapride and esomeprazole decreases the number of RE in anesthetized dogs, but administration of esomeprazole alone was associated with nonacid and weakly acidic reflux in all but 1 dog.