Kotaro Ozasa

Leptin Is Associated with an Increased Female Colorectal Cancer Risk: A Nested Case-Control Study in Japan

Objective: To elucidate whether leptin is involved in the etiology of female colorectal cancer. Methods: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. Results: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, CI: 0.41–4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29–18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. Conclusion: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI.

Dietary Habits and Risk of Lung Cancer Death in a Large-scale Cohort Study (JACC Study) in Japan by Sex and Smoking Habit

Lung cancer has increased and is the leading cause of cancer death among Japanese males. The associations of dietary habits with the risk of lung cancer death were evaluated by sex and smoking habits in this study. In the Japan Collaborative Cohort (JACC) Study, a cohort established in 1988–90 and consisting of 42 940 males and 55 308 females was observed for lung cancer deaths up to the end of 1997. During the observation period, 446 males and 126 females died of lung cancer. A self‐administered food frequency questionnaire was used as the baseline survey. Hazard ratios for dietary factors were calculated by Coxs proportional hazards model. Among males, a high intake of ham and sausages, cheese, green‐leafy vegetables, oranges, and other fruits significantly and dose‐dependently decreased the risk of lung cancer death. Among females, a high intake of miso‐soup, ham and sausages, and liver significantly and almost dose‐dependently increased the risk. Vegetables and fruits rich in antioxidative and carcinogenic agents reduced the risk of lung cancer deaths among male smokers more than among female nonsmokers. The results among female nonsmokers were partially consistent with the hypothesis that high fat consumption increases the risk of lung cancer, especially that of adenocarcinoma.

Attributable and absolute risk of lung cancer death by smoking status: findings from the Japan Collaborative Cohort Study.

Estimating the proportion of lung cancer deaths that can be avoided is important in assessing the potential impact of antismoking efforts on the reduction of lung cancer deaths. We calculated the population attributable risk (PAR) and absolute risk of lung cancer death according to smoking status based on the Japan Collaborative Cohort (JACC) Study. The analytic cohort included 45,010 males and 55,724 females aged 40–79 years. Cox proportional hazards model was used to determine age‐adjusted relative risks and PAR according to smoking status. We also computed lung cancer mortality according to age and smoking status. In males, 52.2% and 14.8% of lung cancer deaths were attributable to current and former cigarette smoking, respectively. In females, the corresponding figures were 11.8% and 2.8%. Among current male smokers, the relative risk was strongly correlated with the intensity and duration of cigarette smoking. In contrast, the PAR was associated with an intermediate level of smoking except for the years of smoking: the largest PARs were observed in those with 20–29 cigarettes per day, 40–59 pack‐years and 20–22 years old at starting smoking. Absolute risks were estimated to increase with age and duration of smoking and not to decrease even after cessation. These findings suggest that avoidable lung cancer deaths are primarily among light to moderate smokers who are considered amenable to population‐based antismoking strategies. For all current smokers, immediate cessation is encouraged because it offers the only realistic way to avoid a substantial increase in lung cancer mortality brought about by further continuation of smoking.

Serum carotenoids and mortality from lung cancer: a case-control study nested in the Japan Collaborative Cohort (JACC) Study

To investigate whether high serum levels of carotenoids, tocopherols, and folic acid decrease risk of lung cancer in Japanese, we conducted a case‐control study nested in the Japan Collaborative Cohort (JACC) Study. A total of 39 140 subjects provided serum samples at baseline between 1988 and 1990. We identified 147 cases (113 males and 34 females) of death from lung cancer during an 8‐year follow‐up. Of the subjects who survived to the end of this follow‐up, 311 controls (237 males and 74 females) were selected, matched to each case of lung cancer death for gender, age and participating institution. We measured serum levels of antioxidants in cases of lung cancer death and controls. Odds ratios (ORs) for lung cancer death were estimated using conditional logistic models. The risk of lung cancer death for the highest quartile of serum α‐carotene, β‐carotene, lycopene, β‐cryptoxanthin, and canthaxanthin was significantly or marginally significantly lower than for the lowest quartile: the ORs, adjusted for smoking and other covariates, were 0.35 (95% confidence interval (Cl), 0.14–0.88), 0.21 (0.08–0.58), 0.46 (0.21–1.04), 0.44 (0.17–1.16) and 0.37 (0.15–0.91), respectively. The ORs for the highest serum levels of zeaxanthin/lutein and folic acid tended to be low, but the differences were not statistically significant. Serum total cholesterol was also inversely related to risk of lung cancer death: the OR for the highest vs. the lowest quartile was 0.39 (95% Cl, 0.19–0.79). Higher serum levels of carotenoids such as α‐ and β‐carotenes may play a role in preventing death from lung cancer among Japanese. (Cancer Sci 2003; 94: 57–63)

Serum Insulin‐like Growth Factors, Insulin‐like Growth Factor‐binding Protein‐3, and Risk of Lung Cancer Death: A Case‐control Study Nested in the Japan Collaborative Cohort (JACC) Study

To elucidate the roles of insulin‐like growth factors (IGFs) in the development of lung cancer, we conducted a case‐control study nested within the Japan Collaborative Cohort Study. Serum samples were collected at baseline from 39 140 men and women between 1988 and 1990. We measured serum IGF‐I, IGF‐II, and IGF‐binding protein‐3 (IGFBP‐3) in 194 case subjects who subsequently died from lung cancer during an 8‐year follow‐up and in 9351 controls. The odds ratios (ORs), adjusted for smoking and other covariates, were smaller with higher levels of IGF‐II and IGFBP‐3. The ORs across quartiles were 0.41 (95% confidence interval [CI], 0.27–0.63), 0.47 (0.31–0.71), and 0.67 (0.46–0.98) for IGF‐II (trend P=0.018), and 0.55 (95% CI, 0.37–0.81), 0.54 (0.36–0.82), and 0.67 (0.45–1.01) for IGFBP‐3 (trend P=0.037). These peptides were not independently related to lung cancer risk when mutually adjusted. The risk was increased in the highest vs. the lowest quartile of IGF‐I only after controlling for IGFBP‐3 (OR, 1.74; 95% CI, 1.08–2.81). Limiting subjects to those followed for ≥3 years strengthened the negative associations of IGF‐II and IGFBP‐3, whereas the ORs for IGF‐I generally decreased. A higher level of circulating IGFBP‐3 and/or IGF‐II may decrease lung cancer risk. Elevated serum IGF‐I may increase the risk, but this could partly be attributable to latent tumors.

Evaluation of Factors Associated With Elevated Levels of Platelet-Derived Microparticles in the Acute Phase of Cerebral Infarction

Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulation-promoting, endothelial cell-activating factors. The objective of this study was to determine the parameters associated with elevated PDMP levels and examine their relationship with atherosclerotic lesions of main intracranial and extracranial arteries. Participants and Methods: Participants included a control group (C) of 61 patients with no apparent cerebral vascular lesions and 110 patients with acute-phase cerebral infarction, consisting of a small-vessel occlusion group (S) of 34 patients, a large-artery atherosclerosis group (L) of 41 patients, a cardioembolism group (CE) of 20 patients, and a stroke of undetermined etiology group (U) of 15 patients. Platelet-derived microparticle levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of admission, and the patients were reclassified into group CP (control level PDMPs), consisting of 70 patients with control PDMP levels, and group HP (high PDMPs), consisting of 40 patients with elevated PDMP levels. All patients underwent cranial magnetic resonance (MR) and carotid ultrasound examinations. Results: Platelet-derived microparticle levels were significantly higher in groups S and L than in group C (P < .01). Concomitant intima-media thickness (IMT; odds ratio [OR] = 1.29, P < .05) and concomitant intracranial stenosis (OR = 3.95, P < .01) were significantly correlated with elevated PDMP levels. Fibrinogen and high-sensitivity CRP levels were significantly higher in group HP than in group CP. Conclusion: Alterations in PDMP levels correlated with the presence of atherothrombotic lesions, and PDMP levels are expected to be useful as a clinical indicator, reflecting the presence of intracranial atherosclerotic lesions in the acute phase of cerebral infarction.

Diabetes mellitus and kidney cancer risk: The results of Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study)

Background:  Diabetes mellitus (DM) is reported as being a risk factor associated with kidney cancer in Western countries. The incidence of both kidney cancer and DM is lower in Japan than the other developed countries, albeit on the rise.

Prevalence and mortality of ulcerative colitis and Crohn's disease in Japan.

SummaryA descriptive epidemiological study of ulcerative colitis and regional enteritis or Crohn’s disease in the general population in Japan was conducted. Mortality rates were based on death certificate records and prevalence rates on the statistics of public aid patients with intractable diseases. Between 1969 and 1985, age-adjusted mortality rates from ulcerative colitis gradually decreased. For regional enteritis, these rates did not change.The prevalence of ulcerative colitis in Japan from April 1, 1984 to March 31, 1985 was 7.85 per 100,000 (6.44 for males, 9.22 for females). The prevalence of Crohn’s disease was 1.86 (2.25 for males, 1.48 for females). These figures are one fourth to one fortieth of the rates in Western countries.

Various S-GOT/S-GPT Ratios in Nonviral Liver Disorders and Related Physical Conditions and Life-Style

The relationship between the GOT/GPT ratio in nonviral liver disorders and underlying physical condition and life-style were evaluated. The subjects were 12,808 male railway company workers who underwent an annual health checkup. Nonviral liver disorders were defined as elevated transaminases (GOT > 76 IU/liter or GPT > 86 IU/liter, while negative for hepatitis B and C markers (282 cases). Controls were 9783 males with normal findings for GOT, GPT, and γ-GTP. By logistic regression analysis, GOT-dominant liver disorders were significantly related to alcohol consumption, hypertriglyceridemia, and diabetes mellitus. They were still significant on multivariate analysis. GPT-dominant liver disorders were significantly related to obesity, less exercise, hypercholesterolemia, and hypertriglyceridemia. Obesity and hypercholesterolemia were significant on multivariate analysis. In conclusion, the relationship between hypertriglyceridemia or diabetes mellitus and GOT-dominant disorders, which was not explained empirically, could indicate another pathogenesis for nonviral liver disorders, such as underlying insulin resistance.

Alcohol consumption and lung cancer mortality in Japanese men: results from Japan collaborative cohort (JACC) study.

BACKGROUND The relationship between alcohol consumption and increased risk of lung cancer is controversial. This study was set up to investigate the association between alcohol consumption and death from lung cancer in a large Japanese cohort. METHODS The subjects comprised 28,536 males, aged 40–79 years, living throughout Japan. During 268,464 person-years of follow-up, 377 lung cancer deaths were recorded. The hazard ratio (HR) of alcohol consumption for lung cancer mortality was calculated using the Cox proportional hazards model after adjustment for age, smoking and family history of lung cancer. RESULTS There was no association between increased mortality from lung cancer and alcohol consumption among current drinkers. Compared with subjects who had never drunk alcohol, the HRs (95% confidence interval [CI]) of death from lung cancer for light (consuming <25.0 g ethanol per day), moderate (25.0–49.9 g per day) and heavy (≥50 g per day) drinkers were 0.81 (95% CI=0.61–1.07), 0.82 (0.61–1.11) and 0.97 (0.66–1.43), respectively. Further adjustment for fruit and vegetable intake did not change the results, and there was no change in HR materially after excluding those patients who died during the first 5 years of follow-up. CONCLUSIONS These findings indicate that alcohol consumption was not associated with increased lung cancer mortality in this population of Japanese men.