Katsuhiro Fukuda

Risk factors of fatality in motor vehicle traffic accidents

The present study was conducted to evaluate the effect of potential risk factors--such as driving without a license, alcohol use, speed, seat belt, and helmet--use on fatality in motor vehicle traffic accidents. Unconditional multiple logistic regression analysis was employed to take these factors and age into account, simultaneously. The effect of driving without a license was not significant after controlling for other factors. The deleterious effect of alcohol use remained significant for male motorcar drivers after controlling for speed and seat belt use. Magnitude of the risk due to speed was slightly reduced after controlling for alcohol use and seat belt use, but the striking effect remained highly significant. Speed was the strongest risk factor of fatality for both motorcycles and motorcars and for both sexes and seemed to be more critical for motorcyclists than motorcar drivers. The protective effect of seat belt use was unchanged after adjustment for alcohol and speed, and the effectiveness of seat belt use was demonstrated for motorcar drivers. The effectiveness of helmet use for male motorcyclists was dependent upon speed at the time of the accidents, suggesting an interaction between helmet use and speed. Helmet use was definitely protective at a low speed of < or = 50 km/h, but ineffective at high speeds of over 50 km/h.

Exposure-response relationships between woodworking, smoking or passive smoking, and squamous cell neoplasms of the maxillary sinus

A case-control study of squamous cell neoplasms of the maxillary sinus was performed in Hokkaido during 1982–86, with 169 cases and 338 controls matched for sex, age, and residence. The data were analyzed by a stepwise forward-telection method based on a conditional logistic-regression model without interaction terms, log-likelihood ratio tests, and chi-square tests for trend. Statistically significant linear trends were observed for associations between the risk of squamous-cell maxillary-sinus neoplasms and the duration of woodworking among men, the daily or lifetime amount of smoking among men, and the number of smokers in the household as an index of domestic exposure to cigarette smoke among women.

Risk factors for hepatocellular carcinoma among Japanese women.

To elucidate the risk factors for hepatocellular carcinoma (HCC) among women, we made a combined analysis of the data from three case-control studies conducted in high-risk areas of Japan. A total of 120 cases and 257 controls were included in the analysis. After adjustment for the study category, age, and other potential confounders, significantly increased risks were associated with chronic hepatitis-B virus infection (odds ratio [OR]=42.4, 95 percent confidence interval [CI]=11.2–160.2), a past history of blood transfusion (OR=3.7, CI=1.8–7.5), and a history of smoking (OR=2.2, CI=12–4.1). In addition, women with a history of heavy drinking experienced an elevated risk of borderline significance (OR=4.2, CI=0.9–20.4, P=0.07). When these ORs were compared with the corresponding estimates among males from the same case-control studies, no significant differences were observed between the two genders. Among the factors examined in this analysis, drinking and smoking habits—which are more common among Japanese men than women—may partly account for a large male-predominance in the incidence of HCC. Further studies are needed to clarify the roles that sex-hormones and hepatitis-C virus infection might play in the large gender difference of HCC occurrence.

World Cancer Research Fund/American Institute of Cancer Research 1997 Recommendations: applicability to digestive tract cancer in Japan

Objectives: This paper reviewed analytic epidemiological studies of the major Japanese digestive tract cancers, i.e. esophageal, stomach, colon and rectal. The applicability of the recommendations for prevention of these cancers by the World Cancer Research Fund/American Institute of Cancer Research (W&A) to Japan is considered.Methods: Papers were searched by the MEDLINE for the period 1966 through 1997. Among them, 43 relevant papers including data from Japan were reviewed.Results: Results for 11 lifestyle-related factors were considered. Cigarette smoking was a strong and consistent, thus, convincing, risk factor for esophageal cancer, and a possible risk factor for stomach and colorectal cancer. Excessive consumption of alcohol was a convincing risk factor for esophageal cancer, and a possible risk factor for stomach and colorectal cancer. Excessive salt intake was a risk factor supported by some strong evidence but inconsistent; therefore, it is a probable risk factor for stomach cancer and a possible risk factor for colorectal cancer. Low physical activity was a probable risk factor for colorectal cancer. On the other hand, sufficient intake of vegetables, including green–yellow vegetables, and fruits was regarded as a possible protective factor for these cancers.Conclusions: These observations were mostly consistent with those reported by W&A; therefore the recommendations by W&A for prevention of these cancers may be considered applicable to the current Japanese population.

Risk of death due to hepatocellular carcinoma among drinkers and ex-drinkers. Univariate analysis of JACC study data.

Hazard ratios (HR) of death due to hepatocellular carcinoma (HCC) were analyzed by gender and age strata (40-59 and 60-79) among drinkers and ex-drinkers in 66,974 eligible subjects from a a large cohort of male and female subjects aged 40-79 years, based on information about several drinking related characteristics. The HR of dying from HCC for ex-drinkers was 4 to 8 times higher than for those who had never consumed alcohol at the baseline survey. When the subjects were restricted to those without history of liver disease (LD), the HR was still high for ex-drinkers among younger males, though the difference was not statistically significant. It appeared that the earlier drinking habits were established, the higher the HR, especially for younger males without LD. Among total current drinkers, the amount ingested per occasion and the cumulative amount ingested at the baseline did not show significantly increased HRs. Among subjects without LD, larger amounts ingested per occasion and larger cumulative amount seemed to have higher HRs in older male current drinkers. Frequent drinking and later age (50 to 79) at cessation of drinking were associated with higher HRs among both genders and both age strata. After restricting the analysis to subjects without LD, many of these increased HRs remained among males. The results suggested that the association between alcohol drinking history and HR of HCC differs depending on the presence of LD. Major confounders other than age and gender associated with both drinking and HCC, e.g. smoking, hepatitis virus infection, or history of diabetes, were not considered in this analysis, and the observed associations might be confounded by any of these factors. To clarify the net association between alcohol drinking and HCC, further analysis is needed to control potential confounders, including past history of liver disease, and to consider probable effect modifiers.

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes and male alcohol use disorders in Khon Kaen, north-east Thailand

Abstract A case–control study on the relationship between alcohol dehydrogenase‐2 (ADH2), aldehyde dehydrogenase‐2 (ALDH2) and male probable alcohol use disorders (AUD) was performed in Khon Kaen, north‐east Thailand. One hundred and fifty‐three paired cases (probable AUD) and controls (non‐probable AUD) were sampled from villagers aged 18–65 years using the modified Michigan Alcoholism Screening Test − Thai version, controls being matched for gender, age (± 4 years) and village. All of the cases and 86.9% of the controls were current drinkers. The percentage of ADH2*1/1 among cases was 47.1%, being significantly larger than the 29.4% among controls, and yielding a univariate odds ratio (OR) of 2.421* (95% confidence interval (CI) = 1.419–4.132) for developing probable AUD. The ALDH2*1/1 proportion among cases, 92.8%, was comparable to the 92.2% among controls, yielding a univariate OR of 1.100 (95%CI = 0.757–1.599). Multivariate analysis based on a conditional logistic regression model and a hierarchically well‐formulated model strategy revealed that: (i) the OR of developing probable AUD due to 1 g increment of daily ethanol drinking was 1.110* among farmers (95%CI = 1.054–1.170); (ii) OR due to 1 g increment of daily ethanol drinking was 1.329* among non‐farmers (95%CI = 1.109–1.593); (iii) OR due to either ADH2*1/1 or ALDH2*1/1 was insignificant; and (iv) the daily amount of smoking is independently associated with probable AUD. The present findings suggest that one of the genetic factors that may be related to probable AUD among Thai males living in the north‐east is the ADH2 gene.

Aldehyde dehydrogenase genotypes and male alcohol use disorders: A case-control study in Khon Kaen, north-east Thailand

A genetic epidemiological case‐control study on aldehyde dehydrogenase 2 (ALDH2) genotype and male probable alcohol use disorders (AUD) was performed in Khon Kaen province, north‐east Thailand. One hundred and twenty‐four of cases (probable AUD) were obtained from male villagers aged 18–65 years using the modified Michigan Alcoholism Screening Test‐Thai version. The same number of controls were selected, being matched with the cases in terms of age (±4 years) within the same village. Marital status, education history and past or present histories of physical illnesses were essentially the same for the cases and the controls. All of the cases and 85.5% of the controls were current drinkers, and the cases tended to drink significantly more often than the controls. Genomic DNA was extracted from fingernails and ALDH2 genotypes were determined by polymerase chain reaction technique and digested by Ksp 632I. The ALDH2 genotypes of the cases and the controls were not significantly different: 90.3% versus 91.1% normal homozygote; 8.1% versus 8.9% heterozygote; and 1.6% versus 0.0% mutant homozygote, respectively. Among the normal homozygote, the daily amount of alcohol intakes of the cases were significantly larger than that of the controls (56.2 ± 40.6 g vs 8.1 ± 14.1 g), the same was found among the ALDH2 deficient (55.9 ± 43.4 vs 2.2 ± 5.8 g). Multivariate analysis based on the conditional logistic regression model showed no significant association of AUD with ALDH2 genotype, marital status, education history, or past history of injury, however, occupation and daily amount of alcohol intake were found to be significantly associated with AUD (OR = 10.72, 95% CI = 1.15 − 99.99, p = 0.037, and OR = 1.12, 95% CI = 1.06 − 1.18, p = 0.000, respectively). Non‐farmers showed 10.7 times larger risk of developing AUD compared to farmers, and the subjects had three times more chance of developing AUD for each increase of 10 g of the daily amount of alcohol intake.

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese.

Abstract  The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case–control study was performed on 153 male Japanese AUD patients and age‐, gender‐, or other confounder‐matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well‐formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026–1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

Simultaneous genotyping of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 by single-strand conformation polymorphism analysis.

Alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) have important roles in the elimination of ingested ethanol. These enzymes have polymorphisms resulting from single‐point mutations that cause kinetic differences in their respective enzyme activities. Simultaneous observation of these enzymes would be useful in investigating the association between these enzyme polymorphisms and alcohol‐related problems. In this study amplified genomic DNA was amplified from nail clippings with two sets of primers for ADH2 and ALDH2 genes, respectively, in a micro test tube and the accuracy of the amplification was verified by direct sequencing. The PCR products were separated into four distinct bands by single‐strand conformation polymorphism analysis. This genotyping method is fast, accurate, reliable and inexpensive, and requires the same amount of template DNA as non‐simultaneous methods. In other words, the required amount of template DNA for this method is only half that required for the separate genotyping of ADH2 and ALDH2.

Dietary survey methods in analytic epidemiology.

慢性疾患の分析疫学的研究に資する目的で, 種々の食習慣調査方法が開発され工夫されてきたが, 潜伏期間が長いこと, 個体差が大きいこと, 食習慣が多面にわたることなどのため, 実用的で妥当で再現性の高い方法を特定するのはむずかしい。食習慣の多様化と年次的変化は食習慣と疾患との関係をいっそう複雑なものにしており, 食習慣調査方法とその性能に関して今後の研究が大いに望まれる分野である。