Satoshi Honjo

Genetic and environmental determinants of risk for cholangiocarcinoma via Opisthorchis viverrini in a densely infested area in Nakhon Phanom, northeast Thailand

Infection with Opisthorchis viverrini (OV) is associated with cholangiocarcinoma. OV is common in northeast Thailand, but less than 10% of the inhabitants develop cholangiocarcinoma. Animal experiments suggest that OV infection alone does not cause cholangiocarcinoma, and thus other environmental and genetic factors may play a role in causation. We conducted a population‐based case‐control study in which sex, age and place of residence were matched individually. Polymorphisms of GSTM1 and GSTT1 alone were not associated with risk for cholangiocarcinoma, while an elevated level of antibodies against OV (ELISA) ≥0.200 was the strongest risk indicator (odds ratio as compared to that <0.200 = 27.09 [95% confidence interval (CI): 6.30–116.57]. Compared to subjects who had a normal antibody range and the wild‐type GSTM1 gene, those who had elevated antibodies had higher odds ratios of 12.32 (95% CI: 1.60–94.85) for wild‐type GSTM1 and 23.53 (95% CI: 4.25–130.31) for the null variant thereof, respectively. Past and current regular drinkers of alcohol had higher risk [odds ratio = 5.39 (95% CI: 1.11–26.06) and 4.82 (95% CI: 1.29–18.06), respectively]. Eating fermented products was an independent risk factor. Smokers or consumers of fermented fish had substantially increased risk if they were past or current drinkers. Infection with OV correlates strongly with cholangiocarcinoma, susceptibility to which may be possibly associated with GSTM1 polymorphism. Alcohol may affect metabolic pathways of endogenous and exogenous nitrosamines.

Epidemiology of Gallbladder Polyps: An Ultrasonographic Study of Male Self-Defense Officials in Japan

The prevalence and risk factors of gallbladder polyps diagnosed by ultrasonography were investigated in 2739 male self-defense officials who received a retirement health examination at the Self-Defense Forces Fukuoka Hospital, Japan, between October 1986 and December 1990. Excluding 38 men whose gallbladder had been removed previously, 143 men were found to have gallbladder polyps. The overall prevalence of gallbladder polyps was 5.3%. The relation between gallbladder polyps and smoking, alcohol use, body mass index, glucose tolerance, and serum lipids was examined in 137 men with stoneless polyps and 2495 normal subjects. Whereas smoking tended to be inversely associated with gallbladder polyps, none of the other lifestyle and clinical variables were related to this condition. Thus the reported risk factors of gallstones had no relation to gallbladder polyps.

Coffee consumption and serum aminotransferases in middle-aged Japanese men

We investigated the relation between coffee drinking and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among 7313 Japanese men receiving a health examination, excluding former alcohol drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol use, smoking, body mass index, serum marker for hepatitis virus infection, and other possible confounders. Adjusted odds ratios of liver inflammation were 1.00 (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5 cups of coffee daily, respectively. Among 6898 men without liver inflammation, serum AST and ALT were inversely associated with coffee consumption, and alcohol-related rise in AST was attenuated with coffee drinking. These findings suggest coffee may have an effect of suppressing the rise of serum aminotransferase, partly by inhibiting the alcohol-related elevation. Studies regarding biological mechanism are warranted.

Obesity and adenomatous polyps of the sigmoid colon

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self‐defense officials who received a retirement health examination at three hospitals of the Self‐Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist‐hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (<5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut‐off points. There was a significant two‐fold elevation in the overall adenoma risk among men at the highest BMI level (≥26.95) compared with those at the lowest level (<22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR: odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4–5.9) for the highest (≥0.958) versus lowest (<0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95%CI 1.5–7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.

Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan.

Post‐transplant outcomes of hemophagocytic lymphohistiocytosis (HLH) patients were analyzed in Japan where Epstein–Barr virus (EBV)‐associated severe forms are problematic.

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

Gallstone disease among Japanese men in relation to obesity, glucose intolerance, exercise, alcohol use, and smoking

BACKGROUND Risk factors for gallstones are not fully understood, especially in men. Obesity and other risk factors for gallstone disease were investigated in Japanese men based on gallbladder ultrasonography. METHODS Forty-one men with gallstones, 31 with postcholecystectomy state, and 2044 with a normal gallbladder were identified among 2228 men aged 49-55 years who received a retirement health examination at three hospitals of the Japan Self-Defense Forces between 1991 and 1992. Glucose tolerance was determined with a 75-g oral glucose tolerance test. RESULTS Body mass index was not associated with gallstones, although it was significantly, positively related to postcholecystectomy. Waist to hip circumference ratio tended to be weakly associated with gallstones. Diabetes mellitus was associated only with postcholecystectomy. Smoking, alcohol intake, and physical activity were not measurably related to either gallstones or postcholecystectomy. CONCLUSIONS The present study failed to substantiate an association of gallstone risk with either obesity or any other risk factor. Further observation is needed in view of the limited study power.

Cigarette smoking, alcohol use and adenomatous polyps of the sigmoid colon.

The relationship of adenomatous polyps of the sigmoid colon with cigarette smoking and alcohol use was investigated in male self‐defense officials in Japan. In the comparison between 116 cases and 930 controls, total ethanol intake was not at all associated with the risk of adenomatous polyps, but cigarette smoking was strongly related to adenomatous polyps. After adjustment for total ethanol intake, body mass index and rank, odds ratios (and 95% confidence interval) for the categories of 0, 1–399, 400–799, and 800 or more cigarette‐years were 1.0 (referent), 2.3 (1.1–4.6), 2.9 (1.5–5.4) and 3.2 (1.6–6.5), respectively. Among five alcoholic beverages (sake, shochu, beer, whiskey including brandy, and wine), only whiskey consumption was weakly related to the risk of adenomatous polyps. Because the present findings disagree with an earlier observation on self‐defense officials, we examined the association with smoking and alcohol use separately for small (<5 mm) and large (≥5 mm) adenomas, combining data from these two studies. Cigarette smoking was more strongly associated with small adenomas while the positive association with certain alcoholic beverages were largely confined to large adenomas. These findings suggest that cigarette smoking and alcohol use may be linked with the development of adenoma at different stages of colon tumorigenesis.

Glucose intolerance and adenomas of the sigmoid colon in Japanese men (Japan)

Objectives: The purpose was to investigate the relation between glucose tolerance and risk of sigmoid colon adenomas, a well-established precancerous lesion, in Japanese men.Methods: In the consecutive series of 7,637 men aged 48 to 59 years who received a preretirement health examination at four hospitals of the Self Defense Forces (SDF) in Japan from 1986 to 1994, we identified 821 cases of sigmoid colon adenomas and 4,372 controls with normal sigmoidoscopy or colonoscopy at 60 cm or more from the anus. Glucose tolerance status was classified as normal, impaired glucose tolerance (IGT), newly diagnosed non-insulin dependent diabetes mellitus (NIDDM), or diabetes mellitus under treatment, based on␣a␣75g oral glucose tolerance test and medical history. Statistical adjustment was made for body mass index (wt/ht2), cigarette smoking, alcohol use, rank of the SDF, and hospital.Results: Modest increases in adenoma risk were observed for newly diagnosed NIDDM and diabetes mellitus under treatment while there was no association between IGT and adenoma risk. When small (< 5 mm in diameter) and large (5+ mm) adenomas were analyzed separately, increased risk associated with newly diagnosed NIDDM was more pronounced for small adenomas, and diabetes mellitus under treatment showed a slightly stronger association with large adenomas.Conclusions: The findings suggest that NIDDM is associated with modestly increased risk of sigmoid colon adenomas, and add to evidence that hyperinsulinemia increases colon cancer risk.

Coffee Drinking and Serum Gamma-Glutamyltransferase: An Extended Study of Self-Defense Officials of Japan

PURPOSE To examine the effect of coffee drinking on serum gamma-glutamyltransferase (GGT) level in relation to alcohol drinking, smoking, and degree of obesity in middle-aged Japanese men. METHODS From 1986 to 1994, a total of 7,637 male officials of the Self-Defense Forces of Japan aged 48-59 years received a preretirement health examination. Coffee drinking was ascertained by a self-administered questionnaire, and serum GGT level was measured. After excluding 1,360 men with a possible pathologic condition influencing liver enzyme levels and 182 former alcohol drinkers, effect of coffee drinking on serum GGT was examined by a multiple linear regression model and analysis of variance adjusting for alcohol drinking, smoking, and body mass index (BMI). RESULTS The adjusted percentage of difference in serum GGT was -4.3 (95% CI = -5.0; -3.5) per cup of coffee. The inverse coffee-GGT relation was most prominent among men drinking > or = 30 ml of ethanol and smoking > or = 15 cigarettes daily; and positive associations of alcohol and smoking with GGT were attenuated by coffee drinking, more clearly among men with BMI > or = 25.00 kg/m2. Adjusted percentages of difference in serum GGT were -2.6% (p = 0.0003) per cup of brewed coffee, and -5.1% (p = 0.0001) per cup of instant coffee, independently of each other. CONCLUSIONS The present study suggests that coffee consumption may weaken GGT-induction by alcohol, and possibly by smoking. These effect modifications by coffee may differ according to the degree of obesity.