Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

Purpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. Results: The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. Conclusion: These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

Relationship between physical activity and locomotive syndrome among young and middle-aged Japanese workers.

OBJECTIVES: This study aimed to examine the relationship between physical activity (PA) and locomotive syndrome (LS) among young and middle-aged Japanese workers. METHODS: This cross-sectional study included 335 participants from a company in Kumamoto, Japan. LS was evaluated using the 25-question Geriatric Locomotive Function Scale (GLFS-25); a GLFS-25 score ≥7 was defined as LS. Weekly PA was measured using the International Physical Activity Questionnaire. Work-related PA (time spent sitting, standing, walking, and strenuous work per day) and sedentary breaks were measured using a Work-related Physical Activity Questionnaire. Screen usage (television [TV], smartphones, tablets, and personal computers) during leisure time was recorded. The association between PA and LS was examined using a multivariate logistic regression analysis adjusted for age, sex, body mass index, history of musculoskeletal disorders, cancer, stroke, occupation, employment type, work time, shift system, employment status, and body pain. RESULTS: A total of 149 participants had LS. Fewer sedentary breaks during work (>70-minute intervals, odds ratio [OR] = 2.96; prolonged sitting, OR = 4.12) and longer TV viewing time (≥180 minutes, OR = 3.02) were significantly associated with LS. In contrast, moderate PA (OR = 0.75) was significantly associated with a lower risk of LS. CONCLUSIONS: Fewer sedentary breaks during work and longer TV viewing time could increase the risk of LS in young and middle-aged Japanese workers.

Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7 ±â€…4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Impact of dietary compositions and patterns on the prevalence of nonalcoholic fatty liver disease in Japanese men: a cross-sectional study.

BACKGROUND: This study aimed to examine the impact of dietary compositions and patterns on nonalcoholic fatty liver disease (NAFLD) morbidity in Japanese men. METHODS: We conducted a cross-sectional study of 281 individuals who underwent comprehensive medical examinations during health screening. Dietary intake was assessed using a semi-quantitative food frequency questionnaire, and factor analysis was performed to detect dietary patterns. NAFLD was diagnosed by the presence of fatty liver on abdominal ultrasonography in nondrinkers (< 30 g/day), and patients were categorized into control (n = 192) and NAFLD groups (n = 89). RESULTS: Compared with the control group, the NAFLD group consumed fewer mushrooms. Three dietary patterns were identified, namely, a healthy pattern, a western pattern, and a snack pattern. The score of healthy pattern was negatively correlated with the risk of NAFLD. Compared with the lowest tertile of the healthy pattern, the middle tertile was associated with a lower risk of NAFLD after adjusting for age, physical activity, and smoking (odds ratio: 0.47, 95% confidence interval: 0.25-0.91). After further adjustments for body mass index, the middle tertile was associated with a lower risk of NAFLD (odds ratio: 0.46, 95% confidence interval: 0.23-0.92). CONCLUSIONS: A healthy dietary pattern comprising frequent intake of seaweeds, vegetables, mushrooms, pulses, and potatoes and starches was associated with a lower risk of NAFLD in Japanese men. In our opinion, this healthy pattern closely resembles the Japanese Washoku diet, indicating that adherence to Washoku may help prevent NAFLD.

Association Between Airflow Limitation and Carotid Intima-Media Thickness in the Japanese Population.

PURPOSE: This study aimed to reveal the association between airflow limitation (AL) and carotid intima-media thickness (IMT) according to smoking status in Japan. SUBJECTS AND METHODS: This cross-sectional study was performed in 2809 subjects, who underwent a comprehensive health examination with pulmonary function tests and carotid ultrasonographic measurement. AL was defined as forced expiratory volume in 1 s/forced vital capacity of <0.7. The subjects were divided into the following four groups: never smokers without AL, never smokers with AL, former/current smokers without AL, and former/current smokers with AL. Mean IMT, the maximum measurable IMT value in the left and right common carotid arteries (IMT-C max), and mean IMT-C max were measured by carotid ultrasonography. The carotid wall thickness as defined as follows: IMT ≥ 1.1 mm (IMT1.1), IMT-C max ≥ 1.2 mm (IMTc1.2), and IMT-C max > 1.5 mm (IMTc1.5), based on each measured region. The association between AL and the carotid wall thickness according to smoking status was assessed by logistic regression analysis. RESULTS: The mean carotid IMT and mean IMT-C max were significantly higher in never smokers with AL and former/current smokers with or without AL than in never smokers without AL. In logistic regression models adjusted for sex, age, body mass index, hypertension, dyslipidemia, hyperglycemia, physical activity, and alcohol consumption, the risk of carotid wall thickness (IMT1.1 [odds ratio {OR}: 1.55; 95% confidence interval {CI}: 1.07-2.24]; IMTc1.2 [OR: 1.52; 95% CI: 1.03-2.24]; IMTc1.5 [OR: 1.99; 95% CI: 1.15-3.46]) were significantly higher in former/current smokers with AL than in never smokers without AL. CONCLUSION: The present results suggest that greater IMT and risk of carotid wall thickness were associated with AL and smoking experience.

Perioperative complications of abdominal surgery in smokers.

PURPOSE: This study examined the association between smoking and perioperative complications of laparoscopic abdominal surgery and whether these complications were reduced with ≥ 4 weeks of preoperative smoking cessation. METHODS: A total of 555 patients who underwent gastric and colorectal cancer surgeries under general anesthesia were divided into the following groups retrospectively: 290 individuals without smoking history (NS group), 144 previous smokers (stopped smoking more than 8 weeks before surgery, PS group), and 121 current smokers (CS group) divided to two groups according to preoperative smoking cessation for < 4 (CS1, n = 76) and 4-8 weeks (CS2, n = 45). RESULTS: When compared with the NS group, postoperative hospitalization duration was significantly longer in the CS1 group (p < 0.01), whereas differences between the CS2 or PS groups and NS group were not significant. The total number of postoperative complications was higher in all groups of smoking than in NS group, independent on preoperative smoking cessation; however, suture failure was significantly more frequent only in CS1 group. Although pack-years did not significantly affect complication rates in smokers, duration of smoking cessation time in PS group was a negative predictor of postoperative complications. CONCLUSION: Providing more than 4 weeks of smoking cessation before gastrointestinal surgery can reduce the duration of hospitalization and rate of suture failure.

Di-(2-Ethylhexyl) Phthalate Promotes Release of Tissue Factor-Bearing Microparticles From Macrophages via the TGFß1/Smad/PAI-1 Signaling Pathway.

BACKGROUND: Plasminogen activator inhibitor type 1 promotes formation of endothelial microparticles with procoagulant activity. However, it remains unclear whether di-(2-ethylhexyl) phthalate, a peroxisome proliferator-activated receptor α agonist, influences microparticle formation. MATERIALS AND METHODS: The effect of di-(2-ethylhexyl) phthalate on release of tissue factor-bearing microparticles was investigated using human M1 macrophages. RESULTS: Exposure of M1 macrophages to di-(2-ethylhexyl) phthalate significantly upregulated expression of plasminogen activator inhibitor type 1, whereas incubation of macrophages with small interfering RNA for peroxisome proliferator-activated receptor α attenuated it. Di-(2-ethylhexyl) phthalate significantly increased the tissue factor protein level in culture supernatants of M1 macrophages, but not M2 macrophages. After purification of proteins by centrifugal filtration, western blotting detected 2 high molecular weight bands of tissue factor-bearing microparticles in culture supernatants of M1 macrophages. The upper band showed binding to factor VIIa and tissue factor pathway inhibitor, unlike the lower band. This suggested heterogeneity of the procoagulant activity of tissue factor-bearing microparticles, presumably dependent upon encryption/decryption of tissue factor. Phosphatidylserine contributes to tissue factor decryption, and western blotting revealed that the density of phosphatidylserine was reduced in the upper tissue factor band compared with the lower band. Di-(2-ethylhexyl) phthalate also upregulated transforming growth factor-ß1 protein production by M1 macrophages. Moreover, silencing of Smad2, Smad3 or Smad4 attenuated plasminogen activator inhibitor type 1 expression and tissue factor-release from macrophages after di-(2-ethylhexyl) phthalate stimulation. CONCLUSIONS: Di-(2-ethylhexyl) phthalate promotes formation of tissue factor-bearing microparticles in human M1 macrophages via the transforming growth factor-ß1/Smad/ plasminogen activator inhibitor type 1 signaling pathway.

Correction to: Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan.

Following publication of the original article [1], the authors reported a correction in the units in the methods section under "Subjects".

Comorbidities according to airflow limitation severity: data from comprehensive health examination in Japan.

OBJECTIVES: The present study aimed to investigate the relationship between airflow limitation (AL) severity and comorbidities in comprehensive health examination. METHODS: This cross-sectional study included 6661 men and 6044 women aged 40-89 who underwent a lung function test during medical checkups. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. Logistic regression analysis was used to assess the association between AL severity and the presence of comorbidities. RESULTS: When compared with the normal lung function group, subjects with AL had a higher prevalence of lung cancer (odd ratio (OR) 9.88, 95% confidence interval (CI) 3.88-25.14) in men, hypertension (OR 1.63, 95% CI 1.26-2.10) in women, diabetes and hyperglycemia (OR 1.23, 95% CI 1.02-1.49 in men, OR 1.61, 95% CI 1.18-2.20 in women) in men and women after adjusting for potential confounders. In men, lung cancer and MetS (the Joint Interim Statement: JIS) were significantly associated with moderate-to-very severe AL after adjustment. In women, hypertension, diabetes and hyperglycemia, MetS (JIS), and MetS (the Japanese Committee of the Criteria for MetS: JCCMS) were significantly associated with mild AL after adjustment. Hypertension was significantly associated with moderate-to-very severe AL after adjustment in women. CONCLUSIONS: Significant relationships were found between AL severity and the presence of comorbid lung cancer in men, hypertension in women, diabetes and hyperglycemia, and MetS in men and women. Knowledge of comorbidities associated with AL should be widely publicized to raise the awareness of chronic obstructive pulmonary disease (COPD).

Association between NAT2, CYP1A1, and CYP1A2 genotypes, heterocyclic aromatic amines, and prostate cancer risk: a case control study in Japan.

BACKGROUND: Heterocyclic aromatic amines (HAAs) may confer prostate cancer risk; however, the evidence is inconclusive and the activity of HAA-metabolizing enzymes is modulated by gene variants. The purpose of our study was to determine whether there was evidence of an association between HAA intake, polymorphisms in NAT2, CYP1A1, and CYP1A2 and prostate cancer risk in Japanese men. METHODS: Secondary data analysis of an observational case control study was performed. Among 750 patients with prostate cancer and 870 healthy controls, 351 cases and 351 age-matched controls were enrolled for analysis. HAA intake was estimated using a food frequency questionnaire and genotypes were scored by TaqMan real-time PCR assay. Logistic regression analysis was conducted according to affected/control status. RESULTS: We found that high HAA intake was significantly associated with an increased risk of prostate cancer (odds ratio (OR), 1.90; 95% confidence interval (95% CI), 1.40-2.59). The increased risk of prostate cancer was observed among individuals with the NAT2 slow acetylator phenotype (OR, 1.65; 95% CI, 1.04-2.61), CYP1A1 GA + GG genotype (OR, 1.27; 95% CI, 1.02-1.59), and CYP1A2 CA + AA genotype (OR, 1.43; 95% CI, 1.03-2.00). In addition, CYP1A1 GA + GG genotypes were associated with increased cancer risk in low (OR, 2.05; 95% CI, 1.19-3.63), moderate (OR, 1.72; 95% CI, 1.07-2.76), and high (OR, 2.86; 95% CI, 1.83-4.47) HAA intake groups. CONCLUSIONS: Our results suggest that high HAA intake is a risk factor of prostate cancer, and genotypes related to HAA metabolic enzymes can modulate the degree of the risk.

Relationship of airflow limitation severity with work productivity reduction and sick leave in a Japanese working population.

BACKGROUND: The aim of this study was to reveal the association between airflow limitation (AL) severity and reduction with work productivity as well as use of sick leave among Japanese workers. METHODS: This cross-sectional study included 1,378 workers who underwent a lung function test during a health checkup at the Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in 1 second/forced vital capacity of <0.7. Workers completed a questionnaire on productivity loss at work and sick leave. The quality and quantity of productivity loss at work were measured on a ten-point scale indicating how much work was actually performed on the previous workday. Participants were asked how many days in the past 12 months they were unable to work because of health problems. Logistic regression analysis was used to assess the associations between AL severity and the quality and quantity of productivity loss at work as well as use of sick leave. RESULTS: Compared with workers without AL, workers with moderate-to-severe AL showed a significant productivity loss (quality: odds ratio [OR] =2.04, 95% confidence interval [CI]: 1.12-3.71, P=0.02 and quantity: OR =2.19, 95% CI: 1.20-4.00, P=0.011) and use of sick leave (OR =2.69, 95% CI: 1.33-5.44, P=0.006) after adjusting for sex, age, body mass index, smoking status, hypertension, hyperglycemia, dyslipidemia, sleep duration, work hours per day, and workplace smoking environment. CONCLUSION: AL severity was significantly associated with work productivity loss and use of sick leave. Our findings suggested that early intervention in the subjects with AL at the workforce might be beneficial for promoting work ability.

XPC intron11 C/A polymorphism as a risk factor for prostate cancer.

OBJECTIVES: DNA repair genes play an important role in protection against environmental and endogenous DNA damage, and constitute the first line of defense against cancer. Xeroderma pigmentosum complementation group C (XPC) is involved in the damage recognition step during nucleotide excision repair. The relationship between XPC intron11 C/A polymorphism and cancer risk has not been widely studied. Hence, this study evaluated the relationship between the XPC intron11 C/A polymorphism and prostate cancer risk. MATERIALS AND METHODS: This hospital-based cohort consisted of 152 patients with prostate cancer and 142 male controls. The XPC intron11 C/A genotype was determined using the PCR-RFLP method. Medical, occupational, and cigarette-smoking history was obtained from each participant using questionnaires. RESULTS: Logistic regression analysis revealed that compared to controls, the frequencies of the A/A and C/A genotypes were significantly higher than those of the C/C genotype in cancer patients (OR = 2.03, 95% confidence interval (CI) 1.03-3.98 and OR = 1.91, 95% CI 1.13-3.24, respectively). We also found that the frequency of the A/A genotype was significantly higher in cancer cases than in controls among non-smokers (OR = 7.7, 95% CI 1.38-42.88, compared to the C/C genotype). CONCLUSION: We found that the XPC intron11 C/A polymorphism was associated with an increased risk of prostate cancer. Among non-smokers, the A/A genotype was significantly more prevalent in prostate cancer patients than in controls.

Associations between aldehyde dehydrogenase 2 (ALDH2) genetic polymorphisms, drinking status, and hypertension risk in Japanese adult male workers: a case-control study.

OBJECTIVES: We sought to identify associations between aldehyde dehydrogenase 2 (ALDH2), alcohol consumption, and hypertension in Japanese men. METHODS: The study participants were 1,225 male Japanese workers. We collected lifestyle information, body measurements, blood biochemical parameters, blood pressure measurements, and ALDH2 genotyping data during medical examinations conducted between March 2004 and January 2005 at a work facility and an affiliated company. Lifestyle data on alcohol intake and smoking were collected using self-administered questionnaires at the same time as when the aforementioned measurements were obtained. RESULTS: The genotype frequencies of ALDH2 genetic polymorphisms were 62.6, 32.7, and 4.7% for *1/*1, *1/*2, and *2/*2, respectively. Systolic blood pressure and diastolic blood pressure in the *1/*2 or *2/*2 group were significantly lower than those in the *1/*1 group (P < 0.001). Multiple regression analysis (stepwise method) for blood pressure according to ALDH2 genetic polymorphism revealed that the amount of daily alcohol intake affected systolic blood pressure in participants who harbored the ALDH2 genetic polymorphism *1/*2 or *2/*2. CONCLUSIONS: The interaction between alcohol intake and ALDH2 genetic polymorphisms might affect systolic blood pressure in adult male workers.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the development and function of the blood-brain barrier.

Prenatal exposure to environmental chemicals such as dioxins is known to have adverse effects on the developing central nervous system (CNS) in mammals. Because the fetal blood-brain barrier (BBB) is immature, dioxins are thought to exert their toxic effects on the CNS by crossing the BBB and acting on neural cells directly. However, little is known whether dioxins alter the BBB. In this study, to investigate the effects of dioxins on BBB function, we exposed an in vitro BBB system comprising rat endothelial cells, astrocytes, and pericytes to the toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either before or after BBB formation. We assessed BBB permeability and the function of tight junctions by measuring transendothelial electric resistance (TEER) values following exposure. Subsequently, total RNA and proteins were obtained from the cells for analysis. TEER values following TCDD exposure before but not after BBB formation were lower than those of the control group. We also observed that the expression of the tight junction proteins ZO-1 and claudin-5 was suppressed following TCDD exposure. To examine the cause of this reduction in protein levels, we performed a real-time quantitative polymerase chain reaction assay and observed low expression of the glial cell line-derived neurotrophic factor (GDNF) mRNA in the exposed groups. Moreover, to rescue the effects of TCDD, we applied extrinsic GDNF with TCDD. The several disruptions caused by TCDD were rescued by the GDNF addition. Our findings suggest that exposure to TCDD during BBB formation disrupts and impairs BBB function in part by the suppression of GDNF action, which may contribute to the adverse effects of TCDD on the fetal CNS.

Association between airflow limitation severity and arterial stiffness as determined by the brachial-ankle pulse wave velocity: a cross-sectional study.

Objective Chronic obstructive pulmonary disease (COPD) is often associated with concomitant systemic manifestations and comorbidities, such as cardiovascular disease. There are limited data regarding airflow limitation (AL) and atherosclerosis in Japanese patients, and the potential association between AL and arterial stiffness has not yet been investigated in Japanese patients. Therefore, the purpose of this study was to investigate the association between AL severity and arterial stiffness using the brachial-ankle pulse wave velocity (baPWV). Methods This cross-sectional study included 1,356 subjects aged 40-79 years without clinical cardiovascular diseases who underwent a comprehensive health screening that included spirometry, the baPWV measurement, and blood sampling during medical check-ups in 2009 at the Japanese Red Cross Kumamoto Health Care Center. AL was defined in accordance with the Global Initiative for COPD criteria (forced expiratory volume in one second / forced vital capacity of < 0.7). A cut-off baPWV value of >1,400 cm/s was used for risk prediction and screening. Results The average baPWV (SD) results were 1,578.0 (317.9), 1,647.3 (374.4), and 1,747.3 (320.1) cm/s in the patients with a normal pulmonary function, mild AL, and moderate-to-severe AL, respectively (p< 0.001). Using logistic regression models adjusted for the age, body mass index, smoking status, hypersensitive C-reactive protein levels, hypertension, hyperglycemia, and dyslipidemia, an increased baPWV (>1,400 cm/s) was significantly associated with moderate-to-severe AL compared with a normal pulmonary function (odds ratio=2.76; 95% confidence intervals, 1.37-5.55; p=0.004). Conclusion Our results indicated an association between AL and increased arterial stiffness. Arterial stiffness may therefore worsen with an increase in the severity of AL.

Associations between estrogen receptor genetic polymorphisms, smoking status, and prostate cancer risk: a case-control study in Japanese men.

OBJECTIVE: Prostate cancer (PCa) is one of the major causes of death among men. Our study investigated the association of ESR1 and ESR2 genotypes with susceptibility to PCa in relation to smoking status in Japanese. METHOD: A case-control study was performed with 750 Japanese prostate cancer patients and 870 healthy controls. After age-matching in case-controls, 352 controls and 352 cases were enrolled in this study. By using logistic regression analysis, the different genotypes from ESR1 and ESR2 were analyzed according to case/control status. RESULT: ESR2 rs4986938 AG and AG + AA genotypes were associated with significantly decreased risk of PCa (AG: OR = 0.68, 95 % CI 0.47-0.97, P < 0.05 and AG + AA: OR = 0.67, 95 % CI 0.47-0.94, P < 0.05). However, there was no significant association between ESR1 rs2234693 and PCa risk. When patients were grouped according to smoking status, the ESR2 rs1256049 AA genotype (OR = 0.48, 95 % CI 0.25-0.95, P < 0.05) and ESR2 rs4986938 AG + AA genotype (OR = 0.64, 95 % CI 0.41-1.00, P < 0.05) showed significantly decreased PCa risk in the ever-smoker group. CONCLUSION: Our results suggest that the estrogen receptor ESR2 has a very important function to predict PCa and that different SNPs have different predictive values. Smoking may influence estrogenic activity and may influence PCa together with the estrogen receptor.

A large cohort study concerning age-dependent impacts of anthropometric variables on spirometric parameters in nonsmoking healthy adults.

BACKGROUNDS: Although height (H) has been considered the principal anthropometric variable governing lung function, the age-dependent differences in its influences on determining spirometric parameters (SPs) have not been conclusively investigated. Moreover, there has been no study centered on age-dependent effects of other anthropometric variables, including body weight (BW) and body fat mass (BFM) on SPs. In addition, the age-dependent influences of these anthropometric variables are anticipated to differ quantitatively between male and female participants. METHODS: A total of 16,919 nonsmoking healthy Japanese adults (men: 6,116, women: 10,803) were partitioned into six groups stratified by gender and age at intervals of 20-years: young-, middle-, and advanced-age groups of either gender. Using a model in which a SP was described by a logarithmic additive function of age, H, BW, and BFM, we determined the partial regression coefficients of the respective anthropometric variables to predict the reference means of SPs, including FVC, FEV1, FEV1/FVC, PEF, FEF50, and FEF75, in the six groups. RESULTS/DISCUSSION: Although the impact of H on FVC and FEV1 was relatively homogeneous irrespective of gender and age, its homogeneity faded for flow parameters, particularly in the female middle- and advanced-age groups, indicating that the age-dependent contribution of H to SPs was enhanced more in women. The impact of BW on SPs differed depending on age, and this effect was also more conspicuous for female participants. H and BW generally exerted positive effects on SPs, whereas BFM had negative effects. Opposite effects of BW and BFM were observed in the female middle-age group in particular. CONCLUSIONS: The effects of anthropometric variables on spirometric parameters are highly age-dependent, particularly in women, leading to the conclusion that the assumption of age-independent, constant partial regression coefficients of anthropometric variables while predicting the reference mean of a certain spirometric parameter may result in substantial errors.

Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population.

OBJECTIVES: Arylamines are considered to be the primary causative agent of bladder cancer in tobacco smokers. To test the hypothesis that variation in the genes that metabolize tobacco carcinogens contribute to bladder cancer, we examined the effects of single nucleotide polymorphisms in the genes of four key enzymes: cytochrome P450 1A2, N-acetyltransferase (NAT) 2, sulfotransferase 1A1, and UDP-glucuronosyltransferase (UGT) 2B7. METHODS: In this study, 282 Japanese patients with transitional cell carcinoma, the most common bladder cancer, and 257 healthy controls were surveyed and compared for frequencies of the genotypes of the four enzymes. Genotypes were determined using PCR-restriction fragment length polymorphism and TaqMan assays. Smoking information was collected by personal interview. Logistic regression analysis and the chi-square test were employed as statistical methods. RESULTS: The NAT2 slow genotype was significantly associated with the risk of bladder cancer [odds ratio (OR) 3.41, 95 % confidence interval (95 % CI) 1.68-6.87; p < 0.05). The NAT2 slow genotype also significantly increased the risk of bladder cancer in heavy smokers (OR 8.57, 95 % CI 1.82-40.25; p < 0.05). Among the different combinations of the four enzyme genotypes, the highest OR (4.20; 95 % CI 1.34-13.14; p < 0.05) was obtained with the NAT2 slow genotype when present in combination with the UGT2B7 *2/*2 or *1/*2 genotype. CONCLUSIONS: Our results suggest that individuals with different genotypes for the enzymes involved in metabolizing carcinogenic arylamines have a different risk of developing bladder cancer. In particularly, the combination of the NAT2 slow genotype with UGT2B7 *1/*2 or *2/*2 genotype is a high risk factor for bladder cancer.