Dose-response relationship between daily step count and prevalence of sarcopenia: A cross-sectional study.

OBJECTIVES: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study included 7949 community-dwelling middle-aged and older adults (aged 45-74 years) from Japan. MEASUREMENTS: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia. RESULTS: The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55-1.11); Q3, 0.71 (95 % CI: 0.49-1.03); Q4, 0.61 (95 % CI: 0.41-0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold. CONCLUSIONS: The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.

Sedentary time, physical activity, and serum SPARC in a middle-aged population.

The influence of habitual physical activity (PA) on the circulating levels of secreted protein acidic and rich in cysteine (SPARC) remains unclear. The purpose of the current study was to clarify the effects of sedentary time, light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA) on the serum SPARC in a general middle-aged population. The current study is a cross-sectional study of 4,000 men and 6,040 women (40-69 years). Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by enzyme-linked immunosorbent assay. Using an isotemporal substitution model, cross-sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analysed according to sex. Interactions with subject characteristics, such as the body mass index (BMI), smoking, and alcohol consumption, were also examined. In men, replacing 60 min of sedentary time with 60 min of MVPA was significantly associated with 23 ng/mL lower serum SPARC levels (confidence interval: -43, -2) after adjusting for confounders, including the BMI (P = 0.028). A significant interaction between replacing sedentary behaviour with LPA and the BMI on SPARC was detected in women (P = 0.029), although the stratified associations for each BMI level (<25 or ≥25 kg/m2) did not reach significance. The current study suggests that replacing sedentary time with MVPA is associated with reduced serum SPARC levels in middle-aged men, but not in women. In addition, a potential interaction between LPA and the BMI on SPARC was also found in women.Highlights An isotemporal substitution analysis showed that replacing sedentary behaviour with moderate- to vigorous-intensity physical activity (MVPA) is associated with decreased serum SPARC levels in men.Such an inverse association between replacing sedentary behaviour with MVPA and the SPARC levels was not observed in women.A potential interaction between replacing sedentary behaviour with light-intensity PA and the body mass index on the serum SPARC levels was also found in women.

Perceived stress, depressive symptoms, and cortisol-to-cortisone ratio in spot urine in 6878 older adults.

BACKGROUND: Late life depression and perceived stress could influence disease pathways via reduced 11ß-HSD2 activity, particularly given suggestions that reduced 11ß-HSD2 activity, which is reflected in the cortisol-to-cortisone ratio, is a risk factor of disease. To date, however, examination of the relationship between the cortisol-to-cortisone ratio and perceived stress or depressive symptoms is insufficient. METHODS: We examined the cross-sectional association of the cortisol-to-cortisone ratio with perceived stress and depressive symptoms, and analyzed whether cortisol levels modify this association, in 6878 participants aged 45-74 years. Cortisol and cortisone in spot urine were measured using liquid chromatography-mass spectrometry. Perceived stress during the past year was measured using a self-reported questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Analyses were performed with adjustment for age, sex, lifestyle factors (smoking habit, alcohol consumption, physical activity, and sleeping hours), and physical health factors (body mass index [kg/m2] and medical history [diabetes, hypertension, and medication for hyperlipidemia or corticosteroids]). RESULTS: Cortisol-to-cortisone ratio and cortisol were positively associated with perceived stress (% change: 2.33, Ptrend = 0.003; and 4.74, Ptrend = 0.001, respectively), but were not significantly associated with depressive symptoms. Further, the relationship between cortisol-to-cortisone ratio and perceived stress was modified by cortisol level and sex: the positive association between perceived stress and the cortisol-to-cortisone ratio was more evident in subjects with lower cortisol levels (Pinteraction = 0.009) and in men (Pinteraction = 0.026). CONCLUSIONS: These findings suggest that the cortisol-to-cortisone ratio in spot urine may be a useful marker for non-acute perceived stress in daily life against a possible background of reduced 11ß-HSD2 in older adults.

Intensity-Specific and Modified Effects of Physical Activity on Serum Adiponectin in a Middle-Aged Population.

CONTEXT: The effects of intensity-specific physical activity (PA) and its interaction with other lifestyle factors on serum adiponectin are currently unclear. OBJECTIVE: To investigate the effects of replacing sedentary time with either light-intensity PA (LPA) or moderate- to vigorous-intensity PA (MVPA) on total and high-molecular-weight (HMW) adiponectin and to examine interactions with smoking, alcohol drinking, coffee consumption, and menopausal status in a general population. DESIGN/SETTING: Cross-sectional study of 4013 men and 6050 women (40 to 69 years of age). MAIN OUTCOME MEASURES: The associations of replacing sedentary time with LPA or MVPA on total and HMW adiponectin were analyzed using an isotemporal substitution model. RESULTS: In men, reallocating 60 minutes of sedentary time to 60 minutes of LPA was associated with 9% and 13% higher total and HMW adiponectin levels even after adjusting for confounders, although such associations were not observed for MVPA. A similar pattern of results was also seen in women. The effect of replacing sedentary time with LPA on adiponectin was clearer in middle/high coffee consumers than in low coffee consumers among women. Although increasing the effect of replacing sedentary time with MVPA on adiponectin was clearer in former/current smokers than in never smokers among men, the replacement effect for MVPA on total adiponectin was clearer in premenopausal women than in postmenopausal women. CONCLUSIONS: Replacing sedentary time with LPA resulted in increased levels of total and HMW adiponectin. The replacement effects for LPA or MVPA were found to be multiply modified by smoking, coffee consumption, and menopausal status.

Perceived Stress, Depressive Symptoms, and Oxidative DNA Damage.

OBJECTIVE: Psychosocial stress may influence the risk of disease through its association with oxidative DNA damage. We examined whether perceived stress and depressive symptoms were associated with urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), with mutual interaction on 8-OHdG. METHODS: This cross-sectional study included 6517 individuals aged 45 to 74 years who participated, between 2010 and 2012, in a follow-up survey of an ongoing cohort study. Perceived stress during the past year was measured using a self-report questionnaire. Depressive symptoms were evaluated using the Zung Self-Rating Depression Scale. Urinary 8-OHdG concentrations were measured using a column switching high-pressure liquid chromatography system coupled to an electrochemical detector. RESULTS: Higher perceived stress was significantly associated with higher 8-OHdG (2.1% increase per one-category increase of stress; ptrend = .025), even after adjusting for sex, age, supplement use, psychosocial factors, psychotropic medication use, smoking, and body mass index. This association was modestly attenuated after further adjustment for physical activity, suggesting possible mediation or confounding by this factor. Depressive symptoms were not significantly associated with 8-OHdG. No significant interaction was detected between perceived stress and depressive symptoms on 8-OHdG. CONCLUSIONS: In a general Japanese population, we found a weak positive association between perceived stress and urinary excretion of 8-OHdG, whereas no association was observed between depressive symptoms and 8-OHdG. Further studies are needed to examine whether the association between perceived stress and 8-OHdG is modified by depressive symptoms.

Intensity-specific effect of physical activity on urinary levels of 8-hydroxydeoxyguanosine in middle-aged Japanese.

Physical activity (PA) is recommended to both promote and maintain health and prevent cancer by improving the body's DNA repair system, which is considered a mechanism of cancer prevention. However, associations between PA and urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), which reflects DNA damage, are unclear. This cross-sectional study included 2370 men and 4052 women aged 45-74 years enrolled between 2010 and 2012. Habitual PA was assessed by single-axis accelerometer and urinary 8-OH-dG levels by automated HPLC. Multiple linear regression analysis was used to examine the relationship between log-transformed urinary 8-OH-dG and total PA (TPA) and PA of moderate/vigorous intensity (MVPA; ≥3 metabolic equivalents), with adjustment for age, body mass index, energy intake, alcohol consumption, smoking status, daily coffee drinking, menopause status (in women), and TPA (for MVPA). On multivariate adjustment, urinary 8-OH-dG levels were inversely correlated with TPA (ß = -0.020, P < 0.01) in women, and this correlation was not changed by PA intensity. Conversely, urinary 8-OH-dG levels were inversely correlated with MVPA (ß = -0.022, P < 0.05) in men, although the correlation with TPA was non-significant. This inverse correlation was clearer in current smokers than in never or former smokers, although the interaction between smoking status and MVPA on urinary 8-OH-dG levels was non-significant. In conclusion, greater TPA in women and greater MVPA in men were correlated with reduction in urinary 8-OH-dG, suggesting sex-specific effects of MVPA and TPA on protection from oxidative DNA damage. Increasing PA may mediate reduction in oxidative stress.

Association between the PPARGC1A polymorphism and aerobic capacity in Japanese middle-aged men.

OBJECTIVE: A lower frequency for the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) Ser482 allele has been reported in elite-level endurance athletes among Caucasians, although this gene polymorphism has not been found to be associated with aerobic capacity in German, Dutch or Chinese populations. The purpose of the current study was to examine the associations between the Gly482Ser polymorphism and aerobic fitness in 112 Japanese middle-aged men. METHODS: The PPARGC1A Gly482Ser polymorphism was identified according to a TaqMan(®) SNP genotyping assay. Habitual physical activity was objectively measured using an accelerometer. The lactate threshold (LT), an index of aerobic fitness, was measured based on a submaximal graded exercise test performed on an electric cycle ergometer. The association between the LT and the Gly482Ser polymorphism was assessed according to a multiple regression analysis and analysis of covariance, with adjustment for potential confounders (age, body mass index, cigarette smoking, physical activity level and regular exercise). RESULTS: A significant association was observed between the PPARGC1A Gly482Ser polymorphism and LT, as carriers of the Ser482 had higher LT values than the Gly482 carriers. CONCLUSION: The current results suggest that the PPARGC1A Ser482 allele is associated with a higher aerobic capacity in Japanese middle-aged men.

Dietary patterns and serum gamma-glutamyl transferase in Japanese men and women.

BACKGROUND: Although specific foods and nutrients have been examined as potential determinants of serum gamma-glutamyl transferase (GGT) concentrations, the relationship between dietary patterns and GGT remains unknown. The present cross-sectional study aimed to determine relationships between dietary patterns and GGT concentrations, and the effects of lifestyle factors on GGT. METHODS: Relationships between dietary patterns and GGT were analyzed in 9803 Japanese individuals (3723 men and 6080 women age 40-69 years) without a history of liver diseases or elevated serum aminotransferase. We examined major dietary patterns by factor analysis of 46 items determined from a validated, short food frequency questionnaire. RESULTS: We defined dietary patterns as healthy, Western, seafood, bread, and dessert. The healthy pattern was inversely related to GGT in men (odds ratio [OR] for highest vs lowest quartile, 0.72; 95% confidence interval [CI], 0.57-0.92; P < 0.01 for trend) and women (OR 0.82; 95% CI, 0.66-1.0; P = 0.05 for trend), whereas the seafood pattern was positively related to GGT in men (OR 1.27; 95% CI, 1.01-1.61; P = 0.03 for trend) and women (OR 1.21; 95% CI, 0.98-1.49; P = 0.05 for trend). Male-specific inverse associations with GGT were found for bread and dessert patterns (OR 0.63; 95% CI, 0.50-0.80 and OR 0.53; 95% CI, 0.41-0.68, respectively; P < 0.01 for both trends). Seafood or bread patterns and alcohol consumption significantly interacted with GGT in men (P = 0.03 and <0.01 for interaction, respectively) and between the dessert pattern and body mass index or smoking habit in women (P = 0.03 and <0.01, respectively, for interaction). CONCLUSIONS: Dietary patterns may be important determinants of GGT, and their possible clinical implications warrant further investigation.

Factors associated with non-participation in a face-to-face second survey conducted 5 years after the baseline survey.

BACKGROUND: Non-participation in second surveys is reported to be associated with certain baseline characteristics; however, such data are unavailable for Japanese populations. Although disease incidence during follow-up might influence participation, few reports have addressed this possibility. This study sought to identify factors associated with non-participation in a second survey of a population-based cohort, and to evaluate the influence of self-reported disease incidence on non-participation. METHODS: After excluding participants who left the area (n = 423), died (n = 163), and withdrew from the study (n = 9) among 12 078 participants in a baseline survey for the Japan Multi-Institutional Collaborative Cohort Study in the Saga region between 2005 and 2007, 11 483 people were invited by mail to participate in a face-to-face second survey between 2010 and 2012. The 5-year clinical health history of non-participants was assessed by mail or telephone. Baseline characteristics and self-reported clinical outcomes of non-participants were compared with those of participants. RESULTS: Among 11 483 people, 8454 (73.6%) participated in the second survey, and 2608 out of 3029 non-participants answered mail or telephone health surveys. Female sex, youngest and oldest ages, lower education, lower occupational class, current smoking, lower physical activity level, shorter sleep time, obesity, and constipation were associated with non-participation. Light drinking (0.1-22.9 g ethanol/day) was associated with participation. Non-participants reported a significantly higher incidence of cancer and a significantly lower proportion of hypertension compared with participants. CONCLUSIONS: Both baseline characteristics and disease incidence during the follow-up period had significant associations with non-participation in the face-to-face second survey.

Objectively measured physical activity and inflammatory cytokine levels in middle-aged Japanese people.

OBJECTIVE: Studies using self-reported physical activity (PA) showed that higher PA is associated with lower circulating levels of C-reactive protein; in contrast, studies investigating associations of objective PA and other inflammatory markers are limited. We investigated cross-sectional associations of accelerometer-determined PA with circulating levels of myokine-type inflammatory cytokines in a middle-aged Japanese population. METHOD: A total of 1838 individuals (737 men and 1101 women) aged 40 to 69 years participated in the baseline survey of a population-based cohort study in Saga, Japan (2005-2007). Habitual PA was assessed by a single-axis accelerometer. Serum interleukin (IL)-4, IL-6, IL-8, IL-15, and tumor necrosis factor (TNF)-α were measured by a multiplex enzyme-linked immunosorbent assay. Associations between PA and cytokine levels were assessed by multiple regression analysis and analysis of covariance, with adjustment for potential confounders. RESULTS: Step count and PA level (PAL) were inversely associated with TNF-α and IL-15 even after adjusting for BMI. Similarly, greater PA indices were also independently associated with a lower level of inflammatory cytokine z score as an index of overall inflammation. CONCLUSION: The current results suggest that greater engagement in daily PA may be linked with reduced levels of myokine-type cytokines including IL-15, irrespective of body weight in middle-aged Japanese people.

Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005. METHODS: We initiated a cross-sectional study to examine associations of genotypes with lifestyle and clinical factors, as assessed by questionnaires and medical examinations. The 4519 subjects were selected from among participants in the J-MICC Study in 10 areas throughout Japan. In total, 108 polymorphisms were chosen and genotyped using the Invader assay. RESULTS: The study group comprised 2124 men and 2395 women with a mean age of 55.8 ± 8.9 years (range, 35-69 years) at baseline. Among the 108 polymorphisms examined, 4 were not polymorphic in our study population. Among the remaining 104 polymorphisms, most variations were common (minor allele frequency ≥0.05 for 96 polymorphisms). The allele frequencies in this population were comparable with those in the HapMap-JPT data set for 45 Japanese from Tokyo. Only 5 of 88 polymorphisms showed allele-frequency differences greater than 0.1. Of the 108 polymorphisms, 32 showed a highly significant difference in minor allele frequency among the study areas (P < 0.001). CONCLUSIONS: This comprehensive data collection on lifestyle and clinical factors will be useful for elucidating gene-environment interactions. In addition, it is likely to be an informative reference tool, as free access to genotype data for a large Japanese population is not readily available.

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.

Interaction between interleukin-1beta -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.

Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice.

The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is very common in East Asian origin. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people with ALDH2*2 because the mutant ALDH2 protein lacks the activity of acetaldehyde metabolism. On the other hand, it is well established that one of the cytochrome P450 enzymes, CYP2E1, is an activator of carcinogens (e.g., nitorosamines) and a generator of oxidative stress, and it is shown that CYP2E1 was induced by ethanol via gene transcriptional regulation. In the present study, to examine the consequences of ALDH2 polymorphism on transcriptional regulation of CYP2E1 in liver tissue, Aldh2+/+ and Aldh2-/- mice were orally administered 5 g/kg body weight of ethanol and the levels of CYP2E1 mRNA in liver tissue then analyzed. The level of CYP2E1 mRNA 12h after the ethanol administration tended to be higher than the 0-h group in Aldh2+/+ mice, however, it was significantly lower than the 0-h group in Aldh2-/- mice. These findings suggest that single-dose ethanol administration downregulates the expression of cytochrome p450 2E1 mRNA in the presence of inactive ALDH2.

Analysis of urinary metabolites of polycyclic aromatic hydrocarbons in incineration workers.

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 mug/gCr, respectively; and the medians of urinary 2NP were 7.5 and 10.0 mug/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.

Lack of aldehyde dehydrogenase ameliorates oxidative stress induced by single-dose ethanol administration in mouse liver.

Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is far more common in East Asian countries. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people who have ALDH2*2, as the mutated ALDH2 lacks acetaldehyde metabolizing activity. On the other hand, it is well established that metabolism of ethanol causes oxidative stress in liver tissue. To examine the consequences of this polymorphism on ethanol-induced oxidative stress in liver tissue, we conducted a study using Aldh2 knockout mice. Aldh2+/+ and Aldh2-/- mice were orally administered ethanol at a dose of 5g/kg body weight. Levels of malondialdehyde, an indicator of oxidative stress, and glutathione, a key antioxidant, in liver tissue were analyzed 0-24h after administration. Levels of malondialdehyde were significantly lower in Aldh2-/- mice than in Aldh2+/+ mice at 12h after injection, while levels of glutathione were higher in Aldh2-/- mice than in Aldh2+/+ mice at 6 and 12h after injection. Our results suggest that a lack of ALDH ameliorates ethanol-induced oxidative stress in liver tissue.

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). CONCLUSIONS: These results suggest that the hOGG1 Ser326Cys polymorphism may not play a major role as an independent factor in hepatocarcinogenesis.

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 >or=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.