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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. A high intake of advanced glycation end products Nε‐carboxymethyl‐lysine was associated with an increased risk of liver cancer in Japanese men. Our finding suggests the potential harmfulness of consuming advanced glycation end products on liver cancer risk.

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.

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. Evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. A prospective study in Japan demonstrated the increased risk of colorectal or colon cancer among men with high intake of red and processed meat. Reduced meat consumption might protect against colorectal cancer.

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. A prospective Japanese cohort study demonstrated the association between exposure to secondhand cigarette smoke from husband and increased risk of breast cancer, with a dose‐response relationship, especially for non‐drinkers. Passive smoking should be consistently considered as a risk factor for breast cancer. The modifying effects of alcohol on increased breast cancer risk from passive smoking need to be confirmed in further studies.

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.

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.

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.

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.