Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study.

CONTEXT: Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE: We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING: Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (ß± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (ß± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (ß± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (ß± SE, -0.192 ± 0.072; P = 0.008). CONCLUSIONS AND RELEVANCE: Children of parents who smoke have evidence of impaired bone health in adulthood.

Association between all-cause and cause-specific mortality and the GOLD stages 1-4: A 30-year follow-up among Finnish adults.

BACKGROUND: Mortality correlates with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria of airway obstruction. Yet, little data exist concerning the long-term survival of patients presenting with different levels of obstruction. METHODS: We studied the association between all-cause and cause-specific mortality and GOLD stages 1-4 in a 30-year follow-up among 6636 Finnish men and women aged 30 or older participating in the Mini-Finland Health Study between 1978 and 1980. RESULTS: After adjusting for age, sex, and smoking history, the GOLD stage of the subject showed a strong direct relationship with all-cause mortality, mortality from cardiovascular and respiratory diseases, and cancer. The adjusted hazard ratios of death were 1.27 (95% confidence interval (CI) 1.06-1.51), 1.40 (1.21-1.63), 1.55 (1.21-1.97) and 2.85 (1.65-4.94) for GOLD stages 1-4, respectively, with FEV1/FVC ≥70% as the reference. The association between GOLD stages 2-4 and mortality was strongest among subjects under 50 years of age at the baseline measurement. Cardiovascular mortality increased consistently for all GOLD stages. CONCLUSIONS: Airway obstruction indicates an increased risk for all-cause mortality according to the severity of the GOLD stage. We found that even stage 1 carries a risk for cardiovascular death independently of smoking history and other known risk factors.

Celiac disease autoimmunity and hip fracture risk: findings from a prospective cohort study.

The impact of celiac disease autoimmunity on bone health is unclear. We investigated the associations of seropositivity for tissue transglutaminase antibodies (tTGA) and endomysial antibodies (EMA) with incident hip fractures using data from a prospective cohort study, Mini-Finland Health Survey. Baseline serum samples, taken in 1978-80, were tested for tTGA and EMA. Incident hip fractures up to the year 2011 were ascertained from a national hospitalization register. Associations between seropositivity and hip fractures were modeled using Cox proportional hazards regression adjusted for age, sex, body mass index, vitamin D, gamma-glutamyl transferase, smoking, and self-rated health. Our analyses were based on 6919 men and women who had no record of celiac disease or hip fracture before the study baseline. A total of 382 individuals had a hip fracture during a median follow-up of 30 years. Compared with the tTGA-negative individuals (n = 6350), tTGA-positive participants (n = 569; with hip fracture, n = 51) had a higher risk of hip fractures (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.17, 2.14). The findings were similar for another tTGA test (n 200; with hip fracture, n = 26; HR = 2.23, 95% CI 1.49, 3.34). We found no evidence for an association between EMA positivity and hip fracture risk (HR = 0.92, 95% CI 0.34, 2.47; n = 74; with hip fracture, n = 4). In our prospective population-based study of Finnish adults, seropositivity for tTGA was associated with an increased hip fracture risk.

Long-term determinants of muscle strength decline: prospective evidence from the 22-year mini-Finland follow-up survey.

OBJECTIVES: To examine long-term changes in handgrip strength and the factors predicting handgrip strength decline. DESIGN: Longitudinal cohort study with 22 years of follow-up. SETTING: Population-based Mini-Finland Health Examination Survey in Finland. PARTICIPANTS: Nine hundred sixty-three men and women aged 30 to 73 at baseline. MEASUREMENTS: Handgrip strength was measured using a handheld dynamometer at baseline and follow-up. Information on potential risk factors, namely lifestyle and chronic conditions, and their changes throughout the follow-up were based on health interviews. RESULTS: Based on linear mixed-effect models, midlife physically strenuous work, excess body weight, smoking, cardiovascular disease, hypertension, diabetes mellitus, and asthma predicted muscle strength decline over 22 years of follow-up (P < .05 for all). In addition, pronounced weight loss, becoming physically sedentary, persistent smoking, incident coronary heart disease, other cardiovascular disease, diabetes mellitus, chronic bronchitis, chronic back syndrome, long-lasting cardiovascular disease, hypertension, and asthma were associated with accelerated handgrip strength decline (P < .05 for all). CONCLUSION: Lifestyle and physical health earlier in life determine rate of muscle strength decline in old age. Efforts should be made to recognize persons at risk in a timely manner and target early interventions to middle-aged persons to slow down muscle strength decline and prevent future functional limitations and disability.

Vertebral fracture and cause-specific mortality: a prospective population study of 3,210 men and 3,730 women with 30 years of follow-up.

INTRODUCTION: Vertebral fractures predict mortality, but little is known about their associations with the causes of death. We studied vertebral fractures for prediction of cause-specific mortality. MATERIAL AND METHODS: A nationally representative sample of 3,210 men and 3,730 women participated Mini-Finland health survey in 1978-1980. Vertebral fractures at the Th1-Th12 levels were identified from chest radiographs at baseline. Cox's proportional hazard model was used to estimate the strength of association between vertebral fracture and mortality. RESULTS: The relative risk (95% confidence interval) of death from natural causes was 1.49 (0.89-2.48) in men and 0.89 (0.60-1.31) in women with vertebral fractures (adjusted for age, body mass index, serum 25-hydroxyvitamin D, educational level, smoking, alcohol intake, physical activity and self-rated general health). Among women the adjusted relative risk of an injury death was 8.51 (3.48-20.77), whereas none of the men with vertebral fracture died due to an injury. CONCLUSION: The patterns of mortality predicted by fracture in the thoracic spine differ between men and women.

Associations of hip osteoarthritis with history of recurrent exposure to manual handling of loads over 20 kg and work participation: a population-based study of men and women.

OBJECTIVES: We reviewed work histories of manual handling of loads >20 kg in relation to hip osteoarthritis by age, exposure and work participation. METHODS: A nationally representative sample of 3110 Finnish men and 3446 women aged 30-97 was recruited. Diagnosis of hip osteoarthritis was based on standardised clinical examination by trained physicians. Previous exposure to physically loading work was evaluated through interviews. Logistic regression was used to estimate associations between work factors and hip osteoarthritis. RESULTS: 1.9% of men and 2.1% of women had hip osteoarthritis. Almost half the men and a quarter of the women had recurrently handled heavy loads at work. Subjects who had manually handled loads >20 kg had a 1.8-fold increased risk of hip osteoarthritis compared to non-exposed references, when age, body mass index, traumatic fractures and smoking were accounted for. Results were similar for men (OR 2.0; 95% CI 1.0 to 4.0) and women (1.8; 1.1 to 2.8). In a sub-analysis of subjects with hip replacement, the OR was 1.7 (1.0 to 2.9). Risk increased first after 12 years' exposure: among men it was 2.2 (0.8 to 5.9) for 13-24 years' exposure, and 2.3 (1.2 to 4.3) for >24 years' exposure. Among women it was 3.8 (1.7 to 8.1) for 13-24 years' exposure. Work participation among men aged <60 years with hip osteoarthritis was 20% lower compared with subjects without osteoarthritis. CONCLUSIONS: A work history of manual handling of loads >20 kg showed a strong association with hip osteoarthritis in all age groups except the youngest.

Skeletal status in psychotic disorders: a population-based study.

OBJECTIVE: To compare the skeletal status of subjects with primary psychotic disorders with the general population by means of bone ultrasound measurements. Schizophrenia seems to be associated with low bone mineral density through a still unclear mechanism, although information on other psychotic disorders is scarce. METHODS: In a nationally representative sample, quantitative ultrasound values of the heel, i.e., broadband ultrasound attenuation (BUA) and speed of sound, were measured from subjects with schizophrenia (n = 48), other nonaffective psychosis (n = 56), affective psychosis (n = 37), and from 6,100 population controls. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision lifetime psychosis diagnoses were based both on Structured Clinical Interview and case note data. Information on the most common risk factors for bone fragility was elicited through an interview, health examination, and questionnaires. In addition, serum 25-hydroxyvitamin D was measured. RESULTS: Women with schizophrenia and men with affective psychosis had significantly lower bone ultrasound values as compared with the age- and sex-matched population controls (Z-BUA = -0.54, p = .001 and Z-BUA = -0.37, p = .04, respectively). Significantly lower vitamin D levels were observed in subjects with schizophrenia in comparison with the general population (p = .006). Schizophrenia remained an independent determinant of poor skeletal status in women even after controlling for common risk factors for osteoporosis, vitamin D status, and antipsychotic and mood-stabilizing medication (Z-BUA = -0.54, p = .002). CONCLUSIONS: In this population-based study, schizophrenia was found to be independently associated with poor skeletal status in women.

Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteoarthritis--a population-based study with a follow-up of 22 years.

OBJECTIVE: Several studies have shown that knee OA is associated with obesity, physical stress at work, traumatic knee injuries, heredity and female gender. However, the body of such evidence comes from cross-sectional or case-control studies, and from only a few follow-up studies, mostly of short duration. Based on the nationwide Mini-Finland Health Survey, we analysed the potential risk factors for prediction of incident knee OA in the long term. METHODS: Focused on major health problems, the survey was carried out in 1978-80 in a sample of 8000 subjects, representative of the Finnish population aged > or =30 years. Altogether 823 subjects free from knee OA at the baseline were re-examined in 2000-01, and after the intervening 22 years 94 new cases of knee OA were found. Knee OA was diagnosed on both occasions by physicians using information on disease histories, symptoms and standardized clinical examinations. RESULTS: The risk of developing knee OA was strongly associated with BMI (kg/m(2)); adjusted for age and gender and other covariates, and compared with the reference category (BMI < 25.0); the relative odds ratios (ORs) with 95% CIs were 1.7 (95% CI 1.0, 2.8) and 7.0 (95% CI 3.5, 14.10) for subjects with BMIs 25.0-29.9 and > or =30.0, respectively. Similarly, the adjusted OR for the heaviest category of physical stress at work was 18.3 (95% CI 4.2, 79.4) compared with the lightest category, and 5.1 (95% CI 1.4, 19.0) for permanent complaints due to past knee injury. CONCLUSIONS: This prospective study confirms the roles of obesity, heavy work load and knee injury in the aetiology of knee OA.

Hip fractures and femoral bone mineral density in male former elite athletes.

INTRODUCTION: We studied whether vigorous physical activity in young adulthood is associated with higher femoral bone density and lower risk of hip fracture at older age in men. MATERIALS: A cohort of former male elite athletes (n=2147) and matched control subjects (n=1467) were studied for their leisure physical activity, and for fragility fractures at the hip (proximal femur) by Cox regression. Areal bone mineral densities (aBMD) at femoral neck and trochanter region were measured using dual-energy X-ray absorptiometry in a subgroup of the former athletes (n=87; median age 59 years) and in a population-based control group (n=194) and compared by general linear models. RESULTS: After their active sporting careers, the former athletes participated in leisure physical activity more than the matched control subjects (p<0.0001). The hazard ratio (HR) of osteoporotic hip fracture adjusted for the occupational group was 0.77 (95% CI 0.45 to 1.32, p=0.34) in the athletes compared with the control subjects. The mean age at the time of the fracture event was 76.9 years (95% CI 73.2 to 78.8) for the athletes and 70.6 years (95% CI 67.1 to 72.9) for the matched control subjects (p=0.005). Adjusted for age and body mass index, aBMD at the proximal femur was significantly higher in the former athletes compared with the population-based control group (p<0.0001 for both measurement sites). CONCLUSIONS: Osteoporotic hip fractures were sustained at a significantly older age among former athletes compared with control subjects. Clear skeletal benefits of long-term physical loading were also observed in comparative DXA measurements of aBMD.

Vitamin D status and the risk of cardiovascular disease death.

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged > or =30 years who were free from CVD at baseline (1978-1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Cox's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

Regular use of traditional analgesics predicts major coronary events: A cohort study.

AIMS: Serious concern has arisen about the cardiovascular safety of selective cyclo-oxygenase-2 (COX-2) inhibitors. However, recent studies have shown that the cardiovascular risks of regular use of traditional analgesics also deserve attention. We investigated the use of traditional analgesics for their prediction of major coronary events during 16 years of follow-up. METHODS: A population sample of 8000 Finns aged 30 years and over was invited to a comprehensive health examination in 1978-1980; 7217 (90%) complied, and 4824 of these had no diagnosed cardiovascular disease. The participants filled in a questionnaire eliciting information on the use of analgesics. Record linkage to the National Hospital Discharge Register and the mortality register of the Central Statistical Office of Finland identified 266 major coronary events (myocardial infarctions or coronary deaths) by the end of 1994. RESULTS: The risk of a major coronary event was significantly elevated among those reporting regular use of analgesics at baseline. Compared with nonusers and adjusted for known risk factors for coronary heart disease, the relative risk of an event during the whole follow-up period was 1.51 (95% confidence interval [CI] 1.08-2.10) among regular users of analgesics. The risk was as high as 5.27 (95% CI 2.13-13.11) during the first two years of the follow-up. Thereafter it leveled off. CONCLUSION: Based on sales statistics almost all analgesics used in Finland at the end of the 1970's were nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, the increased risk of major coronary events among regular users of analgesics is likely to be due to traditional NSAIDs.

Vitamin D status and common risk factors for bone fragility as determinants of quantitative ultrasound variables in a nationally representative population sample.

Calcaneal quantitative ultrasound (QUS) can predict bone strength and fracture risk. Bone fragility has no single cause but results from a complex interplay of several etiologic or contributing factors. Vitamin D is essential for bone health even though it is still unclear how much of this vitamin is required to maintain bone strength and prevent fractures. Measurements of serum 25-hydroxyvitamin D [S-25(OH)D] have indicated a high prevalence of inadequate vitamin D status in a number of studies mostly based on selected study populations. The objective of this study was to examine the associations between S-25(OH)D, common risk factors for bone fragility, and QUS variables in a large unselected population sample. The study population consisted of 2736 men and 3299 women from a nationally representative population sample, aged 30 years or over. Information on lifestyle was elicited by means of interviews and questionnaires. Body fat mass was estimated using an impedance-meter. S-25(OH)D was measured by radioimmunoassay. Calcaneal QUS was performed on the Hologic Sahara apparatus recording broadband ultrasound attenuation (BUA) and speed of sound (SOS). The potential determinants of BUA and SOS were analysed using separate multiple linear regression models for men and women. S-25(OH)D proved to be an independent determinant of BUA (P<0.0001 for men, P<0.001 for women) and SOS (P<0.0001 for men, P<0.05 for women). BUA was also independently associated with age, height, weight, alcohol consumption, and postmenopausal status in women, and with weight, alcohol consumption, smoking and physical activity in men. All of the above variables, except for weight in women, were also found to be independent determinants of SOS in both men and women. A reverse association was found between S-25(OH)D and adiposity in spite of higher intakes of vitamin D in those with higher fat mass. In this unselected sample of men and women, vitamin D status, several lifestyle factors and physical characteristics proved to be significant determinants of BUA and SOS. Inadequate vitamin D status was common, and measures ensuring adequate intakes of vitamin D in the population thus deserve continued attention. Obesity should be taken into account in future assessments of vitamin D status in Finland as in other countries.

Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC(-13910) genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype.

Individual-level measures of social capital as predictors of all-cause and cardiovascular mortality: a population-based prospective study of men and women in Finland.

Individual-level social capital was assessed for prediction of mortality in a nationally representative study population aged 30-99 years at the baseline. A total of 90% of the original sample had participated in a comprehensive health examination (Mini-Finland Health Survey) in 1978-1980. After the first 5 years of the 24-year follow-up period, 1,196 of 3,014 men and 1,280 of 3,689 women died. Individual-level social capital was determined by factor analysis that revealed three factors: residential stability, leisure participation and interpersonal trust. Factor analysis showed a gender difference in leisure social participation. All-cause mortality and cardiovascular mortality were analyzed using Cox proportional hazard models. Adjusted for demographic, life style and biological risk factors, and for health and socio-economic status, leisure participation was associated with reduced all-cause mortality in men (hazard ratio, HR: 0.94; 95% confidence interval, CI: 0.89-1.00). This association seems to be related to economic status in men. Age modifies the effect of interpersonal trust on all-cause mortality in men. In women, leisure participation (HR: 0.96; 95% CI: 0.91-1.00) and interpersonal trust (HR: 0.69; 95% CI: 0.51-0.93) predicted all-cause mortality, and the latter also cardiovascular mortality (HR: 0.93; 95% CI: 0.86-1.00). The associations between individual-level social capital and mortality are gender- and age-related. Understanding the gender and age perspectives appears to be essential for better insight into the interrelations between social capital and health.

Distribution of glutathione S-transferase M1, P1 and T1 genotypes in different age-groups of Finns without diagnosed cancer.

BACKGROUND: Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of hazardous environmental agents, and their polymorphisms may therefore modify the risk of environmentally induced cancers. Consequently, the XME polymorphisms have been extensively studied in this context during recent years. Particular attention has been given to the polymorphisms of glutathione S-transferase (GST) M1, P1 and T1 genes. Previous studies have provided abundant data indicating these polymorphisms as important modifiers of individual susceptibility to cancers of environmental origin. It can be postulated that if the at-risk genotypes of these genes were real risk factors for the environmental cancers, their prevalence would presumably decrease with age in cancer-free part of the population. METHODS: We tested the hypothesis in a population based group of 2105 Finns (1,051 men, 1,054 women) in five age strata (27, 37, 47, 57 and 67 years of age), all without clinically diagnosed cancer. RESULTS: For GSTM1 genotype, a significant interaction was seen between gender and age among never smokers (p=0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31-1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97-2.97) homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the likelihood of being a concurrent carrier of the putatively protective genotypes of all of the three studied GSTs was almost three-fold (OR 2.80, 95% CI 1.10-7.12) in heavy smokers in the two oldest age-groups compared with the other genotypes. CONCLUSIONS: Our findings based on a novel study design provide support to the previous case-control studies suggesting that GST genotypes modify individual risk of environmentally-induced cancers.

Low metacarpal index predicts hip fracture: a prospective population study of 3,561 subjects with 15 years of follow-up.

BACKGROUND: Metacarpal index (MCI), measured from hand radiographs as the ratio between combined cortical thickness and bone diameter, has been suggested for assessment of bone mass and risk of osteoporotic fracture. We studied MCI for its ability to predict hip fractures. METHODS: Hand radiographs were taken and MCI determined in 3,561 subjects from a representative population sample of 8,000 Finns who were 30 years of age or over in 1978-80. Record linkage to the National Hospital Discharge Register identified 117 subjects who had been hospitalized for primary treatment of hip fracture by the end of 1994. RESULTS: High age, low body mass index, tall stature and smoking at baseline showed, independently of each other, significant associations with low MCI. Low MCI was a strong predictor of hip fracture. When adjusted for all potential confounding factors, the relative risk of hip fracture per decrement of MCI by one standard deviation (0.1) was 1.5 (95% CI 1.2-1.8). INTERPRETATION: Low MCI is associated with known risk factors of osteoporosis and predicts hip fracture. Since hand radiographs are easily available at low cost, measurements of MCI can be used as an alternative approach to find osteoporotic individuals with a high risk of hip fracture.

EPHX1 gene polymorphisms and individual susceptibility to lung cancer.

We investigated the roles of EPHX1 Tyr113His and His139Arg polymorphisms in lung cancer susceptibility in a Finnish study population comprising of 230 lung cancer cases and a large control group (n=2105). The controls were distributed into five age strata, which enabled us to examine the potential age-related changes in the putative EPHX1 at-risk genotypes in the cancer free population. Although the exon 3 slow activity associated allele (His113) containing genotypes posed a decreased lung cancer risk compared with the homozygous wild-type Tyr113/Tyr113 genotype (OR, 0.68; 95% CI, 0.49-0.94), no association was seen for the EPHX1 phenotypes interpreted from the combined exons 3 and 4 genotype data. Neither was any difference seen in the prevalence of the EPHX1 Tyr113His genotypes or interpreted EPHX1 phenotypes in the different age groups.

Leisure participation predicts survival: a population-based study in Finland.

The authors study whether leisure participation is an independent predictor of survival over 20 years. Of the nationally representative sample of 8000 adult Finns (Mini-Finland Health Survey), aged >or=30 years, the cohort of 30-59 years (n 5087) was chosen for the Cox proportional survival analyses. The sum score of leisure participation was divided in quartiles (the lowest quartile = scarce = 0-6), two intermediate quartiles = 7-11 and the highest quartile = abundant = 12-21). Adjusted for statistically significant covariates (age, tobacco smoking, alcohol consumption, obesity, self-rated health and diagnosed chronic diseases), and with scarce participation as the reference, the hazard ratios and 95% confidence intervals (CIs) for the risk of death were 0.80, 0.67-0.95 (intermediate) and 0.66, 0.52-0.84 (abundant) for men. The association was insignificant in women with good health. The results show that leisure participation predicts survival in middle-aged Finnish men and its effect is independent of demographic features, of health status and of several other health-related factors. The beneficial effect emphasizes the significance of leisure activities for the promotion of men's health.

Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects.

BACKGROUND AND AIM: According to a widespread hypothesis, antioxidative vitamins and trace elements may protect the body against atherosclerotic diseases, especially in the elderly. We assessed dietary and serum vitamins and minerals for prediction of acute myocardial infarction (AMI) and stroke in elderly subjects. METHODS AND RESULTS: In a population-based health survey with special emphasis on the diet, subjects aged 65-99 years were followed up for up to 10 years. The study population consisted of 361 men and 394 women. Information on individual food consumption was elicited by means of dietary history interviews. Serum vitamins and mineral elements were analysed utilizing commonly applied biochemical methods. Prediction analyses were based on 130 cases accumulated in the AMI group, 70 subjects in the stroke group, and corresponding control subjects. The cases were determined on the basis of revised information from the National Register of Cases of Death, and from the National Hospital Discharge Register. Low intake of vitamin D (p = 0.011) and low serum levels of 1,25-dihydroxy-vitamin D (p = 0.0053) were significantly predictive of stroke when adjusted for age, gender, smoking and functional capacity. On the other hand, high dietary intakes of two flavonoids, luteolin (p = 0.0096) and kaempferol (p = 0.002) were associated with lowered risk of AMI. Furthermore, low serum levels of iron predicted both AMI (p = 0.013) and stroke (p = 0.019). The results remained essentially unchanged when adjusted for additional major risk factors of atherosclerosis. CONCLUSIONS: From the items in the dietary interview, low intakes of vitamin D and certain flavonoids emerged as the sole predictors of AMI and stroke. In biochemical analyses, on the other hand, these disorders were predicted only by low levels of 1,25-dihydroxy-vitamin D and iron in the serum.

Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian population.

CYP2S1 is a recently discovered member of the cytochrome P450 (CYP) gene superfamily. Interestingly, even though the DNA sequence identifies it as the sole member of the new CYP2S family, CYP2S1 exhibits many features typical to CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular substances. These characteristics, together with a wide extrahepatic tissue distribution, suggest that CYP2S1 may have an important role in both exogenous and endogenous metabolism. This is the first study characterising CYP2S1 alleles and naming them with the recommended CYP allele nomenclature. We used denaturing gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which variation was found were examined in subsequent 100 subjects. The coding region of all of the nine exons, as well as a 449 bp fragment of the proximal promoter region, was analysed. This systematic investigation revealed eight single nucleotide polymorphisms (SNPs), which comprise nine different variant alleles (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in the protein-coding areas and one in the proximal 3' untranslated region (3'UTR). Two of these sequence variations (10347C > T and 13106C > T) result in non-conservative amino acid substitutions, i.e. Arg380Cys and Pro466Leu, respectively. The respective allelic variants, CYP2S1*2 ([10347C > T]) and CYP2S1*3 (13106C > T; 13255A > G]), occurred in our study population at frequencies of 0.50 and 3.75%, respectively. The most common of the variant alleles was CYP2S1*1H (23.8%), harbouring a 13255A > G substitution located in the 3'UTR.