Dietary melatonin and liver cancer incidence in Japan: From the Takayama study.

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.

Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study.

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE Nε -carboxymethyl-lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography-tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries. During a mean follow-up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92-3.10), 1.48 (95% CI: 0.77-2.84), and 2.10 (95% CI: 1.10-3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.

Green tea intake and colorectal cancer risk in Japan: the Takayama study.

BACKGROUND: Reportedly, green tea has a preventive effect against colorectal cancer in animal models. Nevertheless, results from epidemiological studies of the association between green tea consumption and colorectal cancer have been inconsistent. We aimed to evaluate colorectal cancer risk in relation to green tea consumption in a population-based prospective cohort study. METHODS: Subjects were 13 957 men and 16 374 women aged ≥35 years in September 1992. The participants' green tea consumption was elicited by administering a food frequency questionnaire. The colorectal cancer incidence was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. Colorectal cancer was defined as the sum of code C18 (colon cancer) and codes C19 and C20 (rectal cancer) according to ICD-10. RESULTS: Up to March 2008, 429 men and 343 women were diagnosed with colorectal cancer. No significant association was found between green tea consumption and colorectal cancer in men and women, respectively. However, for men, compared with the group of 'none or less than once per day' of green tea consumption, the multiple-adjusted relative risks (95% CIs) for colon cancer were 1.32 (0.90, 1.94), 0.76 (0.57, 1.02), and 0.78 (0.49, 1.22), respectively, in the group of 'once per day,' '2-3 times per day', and 'four times per day or more' (trend P = 0.045). CONCLUSIONS: This study observed no overall significant associations between green tea consumption and colorectal cancer risk, except that there was a weak trend for greater consumption of green tea with decreased risk of male colon cancer.

Coffee, Green Tea, and Caffeine Intake and Liver Cancer Risk: A Prospective Cohort Study.

We aimed to investigate whether coffee, green tea, and caffeine intake are associated with liver cancer risk, using data of a prospective cohort study. This study included 30,824 participants (14,240 men and 16,584 women) aged 35 years or older in the Takayama study, which was launched on September 1, 1992. The consumption frequencies of coffee and green tea were assessed using a self-administered questionnaire. Caffeine intake was estimated from the consumption frequencies of caffeine-containing beverages and foods and their caffeine content per serving. The incidence of liver cancer was confirmed using regional population-based cancer registries. During the follow-up period of 16 years, a total of 172 participants developed liver cancer. The adjusted hazard ratios and 95% confidence intervals (CIs) in relation to coffee consumption were 0.65 (95% CI: 0.46-0.93) for less than once per day, 0.63 (95% CI: 0.39-1.02) for once per day, and 0.40 (95% CI: 0.20-0.79) for twice per day or more, compared with nondrinkers. No associations with green tea, black tea and caffeine intake were observed. The present study confirmed that coffee consumption significantly reduces liver cancer risk and raises the possibility that caffeine intake might not account for the association.

Soy Isoflavone Intake and Bladder Cancer Risk in Japan: From the Takayama Study.

Background: There is growing evidence suggesting that soy isoflavones play a protective role in the development of cancer. However, few epidemiological studies have investigated the association between soy isoflavone intake and bladder cancer.Methods: We evaluated the associations of soy and isoflavone intakes with bladder cancer incidence in a population-based prospective study in Japan. Subjects were 14,233 men and 16,584 women age 35 years or older in September 1992. Soy and isoflavone intakes were assessed via a validated food-frequency questionnaire, while controlling for total energy intake. Cancer incidence was mainly confirmed through regional population-based cancer registries. Bladder cancer was defined as code C67 according to the International Classification of Diseases and Health Related Problems, 10th Revision.Results: During mean follow-up of 13.6 years, 120 men and 41 women had developed bladder cancer. After adjustments for multiple confounders, compared with the lowest quartile of soy food intake, the estimated hazard ratios for the second, third, and highest quartiles of soy food intake were 0.74, 0.52, and 0.55, respectively, in men (P-trend: 0.023). The corresponding values were 0.60, 0.75, and 0.64, respectively, in women (P-trend: 0.43). Similar inverse associations were observed between isoflavone intake and bladder cancer risk.Conclusions: A significant decreased risk of bladder cancer was observed among men who had higher intakes of total soy and isoflavones.Impact: Our finding on the potential benefit of consuming soy foods against bladder cancer is promising and warrants further studies. Cancer Epidemiol Biomarkers Prev; 27(11); 1371-5. ©2018 AACR.

Association of alcohol consumption with the risk of stomach cancer in a Japanese population: a prospective cohort study.

Biological studies have provided confirmation of alcohol-related carcinogenesis in the stomach, but the association between alcohol consumption and the risk of stomach cancer remains controversial. We aimed to investigate whether quantitative alcohol intake is associated with the risk of stomach cancer in a large prospective cohort study among a Japanese population. Study participants included 30 714 participants (14 171 men and 16 543 women) aged 35 years or older, who were enrolled in the Takayama study launched on 1 September 1992. Alcohol consumption was assessed quantitatively using a validated food frequency questionnaire. According to alcohol intake (g/day), male participants were classified into quartile groups: Q1, Q2, Q3, or Q4. Female participants were classified into three groups: nondrinkers, and drinkers below or above the median alcohol level. We estimated the hazard ratios and 95% confidence intervals (CIs) for stomach cancer adjusted for age, smoking, BMI, education, total energy intake, salt intake, physical activity, and medical history of diabetes mellitus for each alcohol intake group using the Cox proportional hazards regression model. By the end of March 2008, a total of 678 participants had been diagnosed with stomach cancer. For men, the multivariate-adjusted HRs of stomach cancer for Q2, Q3, and Q4 relative to Q1 were 1.39 (95% CI: 1.07-1.81), 1.35 (95% CI: 1.02-1.79), and 1.38 (95% CI: 1.02-1.87), respectively. In women, no associations were observed. These data suggest that alcohol consumption could be associated with an increased risk of stomach cancer among Japanese men.

Meat consumption and colorectal cancer risk in Japan: The Takayama study.

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population-based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.

Husband's smoking status and breast cancer risk in Japan: From the Takayama study.

The effects of smoking on breast cancer remain unclear. We assessed the associations of subjects' or husbands' smoking status with breast cancer incidence in a population-based prospective study in Japan. The subjects were 15 719 women aged 35 years or older. The follow up was conducted from September 1992 to March 2008. Cancer incidence was mainly confirmed through regional population-based cancer registries. Breast cancer was defined as code C50 according to the International Classification of Diseases and Health Related Problems, 10th Revision. Lifestyle, including smoking status, was assessed with a self-administered questionnaire. Alcohol consumption was assessed with a validated food-frequency questionnaire. After multivariate adjustments for age, body mass index, alcohol consumption, physical activity, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy, active smoking was not associated with the risk of breast cancer. Compared with never smokers whose husband had never smoked, the risks of breast cancer were 1.98 (95% CI: 1.03-3.84) among never smokers whose husband was a current smoker of 21 cigarettes per day or more. The increased risk of breast cancer among women having a smoking husband was pronounced among those who did not habitually consume alcohol. These results suggest that exposure to smoke from husbands is a potential risk factor for breast cancer. The impact of alcohol consumption on the increased breast cancer risk from passive smoking needs to be addressed in further studies.

Soy isoflavone intake and stomach cancer risk in Japan: From the Takayama study.

Although several experimental studies suggested that soy isoflavone intake inhibits the growth of stomach cancer, previous epidemiological studies have observed inconsistent results. We evaluated the associations of soy or isoflavone intake with stomach cancer incidence after considering several lifestyle factors, including salt intake, in a population-based prospective cohort study in Japan. Subjects were 14,219 men and 16,573 women aged 35 years or older in September 1992. Soy and isoflavone intakes, assessed with a validated food-frequency questionnaire, were controlled for the total energy intake. Cancer incidence was mainly confirmed through regional population-based cancer registries. Until March 2008, 441 men and 237 women developed stomach cancer. After adjustments for multiple confounders, a significantly decreased relative risk of stomach cancer was observed in the highest vs. lowest quartile of soy intake; the estimated hazard ratios were 0.71 (95% CI: 0.53, 0.96) for men (p for trend = 0.039) and 0.58 (95% CI: 0.36, 0.94) for women (p for trend = 0.003). Similar inverse associations between isoflavone intake and stomach cancer risk were also observed in women. Higher intake of non-fermented soy foods was significantly associated with a lower risk of stomach cancer (p for trend: 0.022 in men and 0.005 in women), whereas there was no significant association between the intake of fermented soy foods and a risk of stomach cancer. These results suggest that a high intake of soy isoflavone, mainly nonfermented soy foods, have a protective effect against stomach cancer.

Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan.

Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers.

Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study.

The effects of soy or isoflavone intake on breast cancer need to be examined further in epidemiologic studies. We assessed the associations of soy and isoflavone intake with breast cancer incidence in a population-based prospective cohort study in Japan. Participants were members from the Takayama study, aged 35 years or older in 1992. The follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008. Cancer incidence was mainly confirmed through regional population-based cancer registries. Breast cancer was defined as code C50 according to ICD-10. Soy and isoflavone intakes were assessed with a validated food frequency questionnaire. Using the Cox proportional hazard models, the association of soy and isoflavone intake with breast cancer was assessed after adjustments for age, body mass index, physical activity, smoking, alcohol consumption, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy. Among the 15,607 women analyzed, 172 had developed breast cancer. The relative risks of postmenopausal breast cancer were lower among women with higher intakes of soy (trend p = 0.023) and isoflavone (trend p = 0.046), although the relative risks of premenopausal breast cancer were not associated with intakes of soy and isoflavone. Decreased risks of breast cancer were found even among women with a moderate intake of soy and isoflavone. These results suggested that soy and isoflavone intakes have a protective effect on postmenopausal breast cancer.

Chronic neutrophilic leukemia with congenital Robertsonian translocation successfully treated with allogeneic bone marrow transplantation in a young man.

We present a 23-year-old man with chronic neutrophilic leukemia (CNL). Physical examination revealed hepatosplenomegaly. Leukocytosis was evident with predominance of mature neutrophils with basophilic granules. Bone marrow aspiration revealed mature myeloid hyperplasia. Congenital Robertsonian translocation [45,XY,der(13;22)(q10;q10), in all of analyzed 20 cells] was detected; however, cytogenetic and molecular studies for 9:22 translocation were negative. He was diagnosed with CNL and hydroxyurea was started to control his symptoms and white blood cell count. He was then successfully treated with allogeneic bone marrow transplantation (BMT). Although the prognosis of CNL was not determined, curative therapy including allogeneic hematopoietic stem cell transplantation should be attempted in young patients with CNL.

Late-onset neutropenia in patients treated with rituximab for non-Hodgkin's lymphoma.

Late-onset grade 4 neutropenia occurred in 3 (5.6%) of 54 non-Hodgkin's lymphoma patients treated with rituximab between September 2001 and March 2004. Neutropenia appeared 5 to 25 weeks after administration of cytotoxic agents in combination with rituximab and recurred 4 and 17 weeks after the first onset in 2 patients. Five episodes occurred in a total of 332 cycles of rituximab therapy. Bone marrow findings at the time of late-onset neutropenia showed neutrophil maturation arrest with or without reversible myeloid dysplasia in 3 episodes and selective depletion of the myeloid series in 1 episode. Neither circulating immune complexes nor antineutrophil antibodies were detected during the 3 episodes that we evaluated. Bone marrow cells stained CD8- and CD57-. Late-onset neutropenia resolved 5 to 7 days after granulocyte colony-stimulating factor therapy was started. Further studies are needed to determine how rituximab functions and to identify appropriate countermeasures.

CD20-negative pyothorax-associated B cell lymphoma.

We describe an 86-year-old male who developed CD20-negative pyothorax-associated B cell lymphoma 64 years after he had suffered from tuberculous pleuritis. Therapy with 8 courses of THP-COP at 2-week intervals was followed by involved-field radiotherapy of 30 Gy. Uncertain complete remission was achieved. Thereafter, local recurrence of pyothorax-associated lymphoma (PAL) at the primary site was seen. The patient received salvage radiotherapy of 50 Gy. The patient died of pneumonia during a second uncertain complete remission. The progression-free survival and overall survival of this patient were 10 and 15 months, respectively. When compared with the median survival of 9 months reported in the literature, the adverse effect of CD20 negativity on prognosis may not apply to PAL patients with an occasional aberrant phenotype.

Genital ulcers during treatment with ALL-trans retinoic acid for acute promyelocytic leukemia.

Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

[Effective use of TS-1 in a case of advanced gastric cancer, both in treating the tumor and in maintaining the patient's quality of life].

A 60-year-old man was admitted to our hospital suffering from discomfort in the epigastrium. Endoscopic examination revealed stenosis from the fornix to the body of the stomach. The lesion had invaded the lower esophagus. Biopsy specimens confirmed poorly differentiated adenocarcinoma. An abdominal CT scan showed the lesion was a single mass in the stomach and swollen lymph nodes at the fornix, and revealed slight ascites and left hydronephrosis. The patient received oral administration of TS-1. No adverse effect was seen after 3 courses of treatment, and the lesion was reduced so that it was only found in the fornix. During the 1 year and 3 months of treatment with TS-1, this patient worked as mountain guide in the Hida area and was able to travel to the Himalayas in Nepal for the New Year of 2001. To preserve the quality of life of cancer patients, it is worth considering outpatient treatment with TS-1.