Mikako Horita

Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population.

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene–alcohol interactions on HCC risk remain to be elucidated. We conducted a case‐control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two‐pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming ≥3 “go”s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3–54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5–19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 “go”s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene–alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.

Association Between Dietary Pattern and Serum C-Reactive Protein in Japanese Men and Women

Background Dietary pattern may influence the risks of cardiovascular disease, atherosclerosis, type 2 diabetes, and metabolic syndrome through its effects on inflammation. We evaluated the association between dietary pattern and serum high-sensitivity C-reactive protein (hs-CRP) in a Japanese population. Methods In this cross-sectional analysis, we used baseline data from 3905 men and 5640 women (age 40–69 years) who participated in a population-based cohort study between November 2005 and December 2007. Participants with possible inflammation-related diseases, current analgesic use, high hs-CRP levels (≥3000 ng/mL) or extreme dietary energy intake were excluded. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. Results We identified 5 dietary patterns: healthy (high in vegetables and fruit), Western (high in meat and fried foods), seafood (high in shellfish, squid, fish, etc.), bread (high in bread and low in rice), and dessert (high in confections and fruit). After adjustment for age, alcohol use, smoking, physical activity, and body mass index, hs-CRP levels in men were inversely associated with the healthy, bread, and dessert patterns (P-trend: 0.01, 0.06, and <0.01, respectively) and positively associated with the seafood pattern (P-trend = 0.02). In women, hs-CRP levels were inversely associated with the healthy pattern (P-trend = 0.06) and positively associated with the Western pattern (P-trend = 0.06). Conclusions The healthy dietary pattern may be associated with suppressed inflammation in Japanese men and women, independently of body mass index and other factors. The sex-specific associations of hs-CRP with other dietary patterns (eg, the seafood pattern) require further study.

Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population

Limited epidemiological evidence suggests that genetic polymorphisms of drug-metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be involved in tobacco-related hepatocarcinogenesis. We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group. However, we found a significant interaction (P = 0.0045) between CYP1A2 -3860G>A polymorphism and current smoking on HCC risk when we compared HCC cases with CLD patients; adjusted odds ratios [ORs; and 95% confidence intervals (CIs)] for G/A and A/A genotypes relative to G/G genotype were 0.28 (0.12-0.66) and 0.18 (0.04-0.94), respectively, among current smokers (P trend = 0.002), as compared with 1.28 (0.80-2.06) and 0.76 (0.34-1.71), respectively, among never/former smokers (P trend = 0.96). Similarly, in CYP1A2 G/G genotype, significant risk increase was observed for current smoking (OR = 4.08, 95% CI = 2.02-8.25) or more recent cigarette use (e.g. pack-years during last 5 years, P trend = 0.0003) but not in G/A and A/A genotypes combined (OR for current smoking = 1.39, 95% CI = 0.63-3.03; P trend for pack-years during last 5 years = 0.40). These results suggest that the CYP1A2 -3860G>A polymorphism modifies the smoking-related HCC risk among CLD patients.

Factors influencing participation rate in a baseline survey of a genetic cohort in Japan.

Background Although many studies have examined factors that influence the response to postal questionnaires, few have addressed baseline recruitment for cohort studies involving genetic analyses. The aim of this study was to describe the method used for a baseline survey, the Japan Multi-institutional Collaborative Cohort Study (J-MICC Study), in Saga Prefecture, and to examine the factors that might influence the recruitment of participants in such studies. Methods The Saga J-MICC Study is an ongoing population-based prospective cohort study of the genetic and environmental interactions associated with lifestyle-related disease. From 2005 through 2007, a total of 61 447 residents between the ages of 40 and 69 were invited by mail to participate in this study. The survey date and time were arranged by telephone. Results Among that population, 31 002 (50.5%) responded and 12 078 (19.7%) agreed to participate. A completed questionnaire and blood pressure and anthropometric data were collected from all participants; blood, DNA specimens, and accelerometer measures were obtained from the great majority of them. Female sex and older age were associated with a higher participation rate. In addition, the convenience of the survey location and the sending of a reminder significantly improved the participation rate (odds ratio, 1.3). Conclusions Our findings suggest that making the survey location as convenient as possible and sending a reminder can both substantially improve participation rate in population-based studies.

Interaction between interleukin-1β −31T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese

The risk of hepatocellular carcinoma (HCC) increases with the severity of hepatic inflammation. Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are proinflammatory cytokines with multiple biological effects and may play essential roles in inflammation-linked tumor development. We conducted a case-control study including 209 incident HCC cases and two control groups (275 hospital controls and 381 patients with chronic liver disease [CLD] without HCC) to investigate whether IL-1B and TNF-A gene polymorphisms influence HCC susceptibility with any interaction with alcohol and tobacco. By comparing HCC cases with CLD patients, we found that IL-1B -31T/C polymorphism was associated with HCC risk among never drinkers and current smokers; adjusted odds ratios (and 95% confidence intervals) for C/T and T/T genotypes compared with C/C genotype were 1.70 (0.76-3.77) and 2.46 (1.05-5.76) (P trend=0.03), respectively, among never drinkers, and 1.53 (0.60-3.99) and 2.54 (0.81-7.95) (P trend=0.11), respectively, among current smokers. Similarly, HCC risk associated with heavy alcohol intake and current smoking differed by this polymorphism among CLD patients. IL-1B -31T/C polymorphism may modify HCC risk in relation to alcohol intake or smoking.

hOGG1 Ser326Cys Polymorphism and Risk of Hepatocellular Carcinoma among Japanese

BACKGROUND The Ser326Cys polymorphism in human oxoguanine glycosylase 1 (hOGG1), which is involved in the repair of 8-hydroxy-2-deoxyguanine in oxidatively damaged DNA, has been associated with susceptibility to certain cancers, but has not been examined in causation of hepatocellular carcinoma (HCC). METHODS We conducted a case-control study to investigate whether this polymorphism was related to HCC risk with any interaction with alcohol consumption and cigarette smoking. Genotyping was performed by a polymerase chain reaction with confronting two-pair primers among 209 newly diagnosed HCC cases, 275 hospital controls, and 381 patients with chronic liver disease (CLD) without HCC. RESULTS Overall, the hOGG1 genotype was not significantly associated with HCC; adjusted odds ratios (and 95% confidence intervals) for the Ser/Cys and Cys/Cys genotypes compared with the Ser/Ser genotype were 0.79 (0.35-1.79) and 0.48 (0.18-1.27) against hospital controls, and 1.51 (0.96-3.37) and 0.86 (0.50-1.47) against CLD patients. We could not detect any significant gene-alcohol interaction (p = 0.95 or 0.16) or gene-smoking interaction (p = 0.70 or 0.69). CONCLUTIONS These results suggest that the hOGG1 Ser326Cys polymorphism may not play a major role as an independent factor in hepatocarcinogenesis.

Analysis of Urinary Metabolites of Polycyclic Aromatic Hydrocarbons in Incineration Workers

Analysis of Urinary Metabolites of Polycyclic Aromatic Hydrocarbons in Incineration Workers: Masayoshi Ichiba, et al. Department of Social and Environmental Medicine, Saga Medical School—Incineration workers are exposed to various pyrolysis products of organic materials, heavy metals and polycyclic aromatic hydrocarbons (PAHs). In this study, the exposure of incineration workers to PAHs was evaluated by measuring urinary metabolites of pyrene and naphthalene. The concentrations of urinary 1‐hydroxypyrene (1OHP), a metabolite of pyrene, and 2‐naphthol (2NP), a metabolite of naphthalene, were measured among 100 workers in 4 different types of incinerators, both before and after their work shifts. These incinerators were two old types, one modern type and one outdoors. The medians of urinary 1OHP of before and after the work shifts obtained from all workers were 0.067 and 0.044 µg/gCr, respectively; and the medians of urinary 2NP were 7.5 and 10.0 µg/ gCr, respectively. A significant increase of 2NP after the work shift was found at one old incinerator. A significant decrease of metabolites was found at the other old incinerator. Significant correlations were found between urinary metabolites and cigarettes smoked per day. The effect of smoking on urinary metabolite levels was also important. Significant correlations were found between urinary 1OHP and 2NP levels in all workers. In multiple regression analysis smoking habit and incinerator type were found as significant factors. The improvement of the work environment, through decreasing exposure to both tobacco smoke and hazardous work shift‐related substances, should be an occupational health aim.

Detailed analysis of Japanese population substructure with a focus on the Southwest Islands of Japan

Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating FST among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study.

Immunogenicity and Safety after Booster Vaccination of Diphtheria, Tetanus, and Acellular Pertussis in Young Adults: an Open Randomized Controlled Trial in Japan

ABSTRACT The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.)

Perceived stress and coping strategies in relation to body mass index: cross-sectional study of 12,045 Japanese men and women.

Background Accumulated evidence suggests a weak positive relationship between psychosocial stress and body mass index (BMI), but little is known about stress coping strategies and BMI. Objective We aimed to examine if perceived stress and coping strategies are related to BMI, with any of their mutual interactions on BMI. Methods This cross-sectional study included 5,063 men and 6,982 women aged 40-69 years. A self-administered questionnaire ascertained perceived stress and 5 items of coping strategies (emotion expression, emotional support seeking, positive reappraisal, problem solving, and disengagement). Analyses were performed by gender with adjustment for age, socioeconomic status, and lifestyle factors. Results No significant associations were detected between perceived stress and BMI in either men (P trend = 0.09) or women (P trend = 0.58). In men, however, ‘disengagement’ showed an inverse association with BMI (P trend < 0.001), and ‘positive reappraisal’ and ‘problem solving’ revealed a positive association with BMI (P trend = 0.04 and 0.007, respectively) even after controlling for perceived stress. A possible interaction between perceived stress and ‘disengagement’ on BMI was found in men (P interaction = 0.027); the inverse association between ‘disengagement’ and BMI was more evident in higher levels of stress (β = −0.13, P trend = 0.21 in low; β = −0.22, P trend = 0.01 in medium; and β = −0.24, P trend = 0.06 in high). In men, ‘disengagement’ was inversely associated with overweight/obesity (odds ratio 0.79, 95% confidential interval 0.67-0.95), and “positive reappraisal” was positively associated with it (1.25, 1.02-1.54). Conclusions Coping strategies may have an important role in developing overweight/obesity, particularly in men.