Associations of inflammatory polyarthritis with clinical and radiological findings of temporomandibular disorders.

OBJECTIVE: To evaluate the association of different forms of inflammatory polyarthritis with clinical signs of temporomandibular disorders (TMD) and radiological findings in temporomandibular joint (TMJ), based on a nationwide health survey in Finland. The aim was also to assess the presence of clinical and radiological TMD findings in subjects with increased risk for developing rheumatoid arthritis (RA). MATERIAL AND METHODS: A nationally representative sample included 6331 Finnish adults who participated in the Health 2000 Survey (BRIF8901). Subjects were examined for signs of TMD, findings in panoramic radiograph of TMJ, musculoskeletal health and serology (rheumatoid factor, RF, and anti-cyclic citrullinated peptide, aCCP). RESULTS: Sixty-four percent of seronegative RA and 60% of seropositive RA subjects had at least one sign of TMD. While adjusting for confounding factors (gender, age, dentures and smoking history), RA was significantly associated with crepitation and abnormal radiological findings in TMJ. Seronegative RA was also associated with restricted mouth opening. Systemic autoimmunity associated with RA ("at risk of RA") was not associated with clinical or radiological TMD findings. CONCLUSIONS: Clinical and radiological findings of TMD are more prevalent among subjects with inflammatory polyarthritis than among the population in general in the Finnish adult population.

Mortality of asthma, COPD, and asthma-COPD overlap during an 18-year follow up.

BACKGROUND: We studied asthma, COPD, and asthma-COPD overlap (ACO) to predict mortality in a cohort of Finnish adults with an 18-year follow up. METHODS: A national health examination survey representing Finnish adults aged ≥30 years was performed in 2000-2001. The study cohort included 5922 participants (73.8% of the sample) with all relevant data, including a comprehensive clinical examination and spirometry. These participants were followed continuously from baseline until end of 2018 for total, cardiovascular, cancer, and respiratory mortality through a record linkage. Asthma, COPD, and ACO were defined based on the survey data, including spirometry and register data. There were three separate groups of obstructive subjects (one definition excluding the others). RESULTS: Asthma and COPD were significantly associated with higher total mortality in Cox's model adjusted for sex, age, smoking, education level, BMI, leisure time physical activity, cardiovascular disease, diabetes, and hypertension. Hazard ratios (HR) (95% confidence interval [CI]) for asthma, COPD, and ACO were 1.29 (1.05-1.58), 1.50 (1.20-1.88), and 1.26 (0.97-1.65), respectively. Additionally, asthma (HR 1.47, 95% CI 1.09-1.97) and COPD (HR 1.53, 95% CI 1.08-2.16) were associated with cardiovascular mortality. Although ACO did not predict mortality in the whole cohort, there was a significant association with mortality risk among those with hs-CRP 1-2.99 mg/l. CONCLUSIONS: Asthma or COPD predicts higher total mortality and premature death from cardiovascular diseases.

Atopic dermatitis in adults: a population-based study in Finland.

BACKGROUND: The prevalence of atopic dermatitis (AD) has increased, but studies in adult or elderly populations are sparse. METHODS: We investigated 12-month and lifetime prevalences of AD in the Finnish adult population ≥30 years of age and analyzed living environment factors, socioeconomic factors, lifestyle-related factors, and serum vitamin D levels for their associations with AD in a national health examination survey. RESULTS: The lifetime prevalence was 21.9% and 12-month prevalence 10.1%. The highest prevalence (lifetime 28.6%, 12-month 15.4%) was seen in subjects 30-39 years of age. Prevalence decreased with age. Subjects with highly educated parents were more likely to have active AD, though there was no effect of higher education in subjects themselves. Younger age and being an ex-smoker were associated with active AD. Female sex and daily smoking increased the risk in subjects 30-49 years of age. There was no dose-response relationship to serum vitamin D levels and no association with the living environment. CONCLUSIONS: Our data show that the number of adult patients with atopic dermatitis has grown and prevalence numbers of AD in Finnish adults are among the highest reported. Together with the aging of the society, the burden of AD is not limited to childhood.

Association between educational level and smoking cessation in an 11-year follow-up study of a national health survey.

Aims: There is a lack of longitudinal, population-based studies on the association between education and smoking cessation. A more thorough examination of this association is needed to address inequalities in smoking. Methods: The longitudinal Health 2000 Survey and Health 2011 Survey, representing the Finnish population aged ⩾30 years, were analysed. Of the 1352 baseline daily smokers, 945 (70%) provided a smoking status at the follow-up. The analytic sample size was 884 (excluding the follow-up occasional smokers). Self-reported questionnaire data and measurements (e.g. plasma cotinine) from the baseline were utilised. The outcome variable was smoking cessation at the follow-up, and the main explanatory variable was education. Logistic regression was the main method for statistical analyses. All of the analyses accounted for the sampling design. Results: At the follow-up, 28% of the baseline daily smokers had quit smoking. An adjusted regression model showed that highly educated respondents had a higher likelihood of quitting smoking compared with those with basic education. Controlling for demographic and health-related variables had a modest effect on this association. Higher scores for plasma cotinine, symptoms of depression and heavy alcohol use were associated with a lower likelihood of quitting smoking. The association between education and smoking cessation was weaker for women than it was for men. Conclusions: High education is associated with smoking cessation among the general adult population, especially among men. A higher plasma cotinine level is strongly associated with continued smoking among both sexes. Background variables only modestly affected the association between education and smoking cessation.

Joint effects of alcohol use, smoking and body mass index as an explanation for the alcohol harm paradox: causal mediation analysis of eight cohort studies.

BACKGROUND AND AIMS: Lower socio-economic status (SES) is associated with higher alcohol-related harm despite lower levels of alcohol use. Differential vulnerability due to joint effects of behavioural risk factors is one potential explanation for this 'alcohol harm paradox'. We analysed to what extent socio-economic inequalities in alcohol-mortality are mediated by alcohol, smoking and body mass index (BMI), and their joint effects with each other and with SES. DESIGN: Cohort study of eight health examination surveys (1978-2007) linked to mortality data. SETTING: Finland. PARTICIPANTS: A total of 53 632 Finnish residents aged 25+ years. MEASUREMENTS: The primary outcome was alcohol-attributable mortality. We used income as an indicator of SES. We assessed the joint effects between income and mediators (alcohol use, smoking and BMI) and between the mediators, adjusting for socio-demographic indicators. We used causal mediation analysis to calculate the total, direct, indirect and mediated interactive effects using Aalen's additive hazards models. FINDINGS: During 1 085 839 person-years of follow-up, we identified 865 alcohol-attributable deaths. We found joint effects for income and alcohol use and income and smoking, resulting in 46.8 and 11.4 extra deaths due to the interaction per 10 000 person-years. No interactions were observed for income and BMI or between alcohol and other mediators. The lowest compared with the highest income quintile was associated with 5.5 additional alcohol deaths per 10 000 person-years (95% confidence interval = 3.7, 7.3) after adjusting for confounders. The proportion mediated by alcohol use was negative (-69.3%), consistent with the alcohol harm paradox. The proportion mediated by smoking and BMI and their additive interactions with income explained 18.1% of the total effect of income on alcohol-attributable mortality. CONCLUSIONS: People of lower socio-economic status appear to be more vulnerable to the effects of alcohol use and smoking on alcohol-attributable mortality. Behavioural risk factors and their joint effects with income may explain part of the alcohol harm paradox.

Associations of Metabolic Syndrome and Its Components with the Risk of Incident Knee Osteoarthritis Leading to Hospitalization: A 32-Year Follow-up Study.

OBJECTIVES: To examine whether metabolic syndrome or its individual components predict the risk of incident knee osteoarthritis (OA) in a prospective cohort study during a 32-year follow-up period. DESIGN: The cohort consisted of 6274 participants of the Mini-Finland Health Survey, who were free from knee OA and insulin-treated diabetes at baseline. Information on the baseline characteristics, including metabolic syndrome components, hypertension, elevated fasting glucose, elevated triglycerides, reduced high-density lipoprotein, and central obesity were collected during a health examination. We drew information on the incidence of clinical knee OA from the national Care Register for Health Care. Of the participants, 459 developed incident knee OA. In our full model, age, gender, body mass index, history of physical workload, smoking history, knee complaint, and previous injury of the knee were entered as potential confounding factors. RESULTS: Having metabolic syndrome at baseline was not associated with an increased risk of incident knee OA. In the full model, the hazard ratio for incident knee OA for those with metabolic syndrome was 0.76 (95% confidence interval [0.56, 1.01]). The number of metabolic syndrome components or any individual component did not predict an increased risk of knee OA. Of the components, elevated plasma fasting glucose was associated with a reduced risk of incident knee OA (hazard ratio 0.71, 95% confidence interval [0.55, 0.91]). CONCLUSIONS: Our findings do not support the hypothesis that metabolic syndrome or its components increase the risk of incident knee OA. In fact, elevated fasting glucose levels seemed to predict a reduced risk.

Does lung function predict the risk of disability pension? An 11-year register-based follow-up study.

BACKGROUND: Spirometry is widely used in medical surveillance in occupational health and as a diagnostic test for obstructive and restrictive lung disease. We evaluated the effect of spirometry parameters on the risk of all-cause disability pension in a follow-up study of an occupationally active general population-based cohort. METHODS: We measured the pulmonary function of 3386 currently working participants of the Health 2000 Survey in the clinical phase at baseline using spirometry. We obtained the retirement events of the cohort from the nationwide register for 2000-2011. Cox proportional hazards models were used to determine disability pensions. RESULTS: At baseline, we identified 111 (3.3%) participants with obstructive spirometry, 95 (2.8%) with restrictive spirometry, and 3180 controls without restriction or obstruction. The age, sex, educational level, body-mass index, co-morbidities (1 or ≥ 2), and the smoking-adjusted hazard ratio of disability pension was 1.07 (95% confidence interval, CI 0.64-1.78) for those with obstructive spirometry, and 1.44 (95% CI 0.89-2.32) for those with restrictive spirometry. As continuous variables, and divided into quartiles, the risk of the lowest quartile of forced ventilation capacity (FVC)% of predicted was 1.49 (95%CI 1.10-2.01) and forced expiratory volume in one second (FEV1)% of predicted 1.66 (95%CI: 1.23-2.24) in comparison to the highest quartile in the adjusted models. CONCLUSIONS: Obstructive or restrictive spirometry did not predict disability pension when dichotomized classified variables (normal compared to abnormal) were used. As continuous variables and when divided into quartiles, lower lung volumes showed an increase in the risk of disability pension. Physicians should take this into account when they use spirometry as a prognostic factor of work disability.

Self-Report Dieters: Who Are They?

Dieting attempts have become popular worldwide. Dieting, however, seems to have both positive and negative health-related consequences. So far, only a few studies have focused on the determinants of dieting in detail. This study explores the association between self-report dieting attempts and intentional weight loss (IWL) during the previous year and several demographic, lifestyle, health, and psychological factors in a cross-sectional study design using data from the representative Finnish Health 2000 Survey. The sample comprised 2147 men and 2378 women, aged 30-69. Information for potential determinants was assembled via health examinations, interviews, and questionnaires. Approximately 24% of the men and 39% of the women reported dieting attempts and 10% of the men and 15% of the women reported IWL. Dieting attempts were associated with younger age, education, BMI, formerly smoking, more favourable values in lifestyle variables, and unfavorable values in serum HDL and triglycerides, a worse sense of coherence, concerns about one's appearance, and concerns about one's health. Among men, diabetics and those sleeping ≤6 h a night more frequently reported dieting attempts and those with osteoarthritis reported IWL. Moreover, the gradient between BMI and dieting attempts was significantly stronger in men than in women. Men seem to attempt dieting when they have actual health-related reasons, while such reasons are not so strongly associated with dieting in women. These findings can be used for determining subpopulations with obesity and real weight-loss needs and, alternatively, subpopulations with normal weight unnecessarily attempting dieting.

Airway obstruction, serum vitamin D and mortality in a 33-year follow-up study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort. METHODS: We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles. RESULTS: Both obstruction and low s-25(OH)D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40-0.80), respectively. CONCLUSIONS: In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.

Risk Factors for Low Back Pain: A Population-Based Longitudinal Study.

OBJECTIVE: To identify risk factors for low back pain (LBP) and lumbar radicular pain and to assess whether obesity and exposure to workload factors modify the effect of leisure-time physical activity on LBP and lumbar radicular pain. METHODS: The population of this 11-year longitudinal study consists of a nationally representative sample of Finns ages ≥30 years (n = 3,505). The outcomes of the study were LBP and lumbar radicular pain for >7 days or for >30 days in the past 12 months at follow-up. RESULTS: LBP and lumbar radicular pain were more common in women than in men. LBP slightly declined with increasing age, while lumbar radicular pain increased with age. Abdominal obesity (defined by waist circumference) increased the risk of LBP (adjusted odds ratio [OR] 1.40 [95% confidence interval (95% CI) 1.16-1.68] for LBP >7 days and adjusted OR 1.41 [95% CI 1.13-1.76] for LBP >30 days) and general obesity (defined by body mass index) increased the risk of lumbar radicular pain (adjusted OR 1.44 [95% CI 1.12-1.85] for pain >7 days and adjusted OR 1.62 [95% CI 1.16-2.26] for pain >30 days). Smoking and strenuous physical work increased the risk of both LBP and lumbar radicular pain. Walking or cycling to work reduced the risk of LBP, particularly LBP for >30 days (adjusted OR 0.75 [95% CI 0.59-0.95]), with the largest reductions among nonabdominally obese individuals and among those not exposed to physical workload factors. Using vibrating tools increased the risk of lumbar radicular pain. CONCLUSION: Lifestyle and physical workload factors increase the risk of LBP and lumbar radicular pain. Walking and cycling may have preventive potential for LBP.

Carpal tunnel release: Lifetime prevalence, annual incidence, and risk factors.

INTRODUCTION: We estimated the lifetime prevalence and incidence of carpal tunnel release (CTR) and identified risk factors for CTR. METHODS: The study population consisted of individuals aged ≥30 years living in Finland during 2000-2001 (N = 6,256) and was linked to the Finnish Hospital Discharge Register from 2000 to 2011. RESULTS: Lifetime prevalence of CTR was 3.1%, and incidence rate was 1.73 per 1,000 person-years. Female sex (adjusted hazard ratio [HR] = 1.8, 95% confidence interval [CI] 1.2-2.8), age of 40-49 years (HR = 2.5, CI 1.7-3.8 compared with other age groups), education (HR = 0.6, CI 0.4-0.9 for high level vs. low/medium level), obesity (HR = 1.7, CI 1.2-2.5 for body mass index ≥30 vs. < 30 kg/m2 ), and hand osteoarthritis (HR = 2.4, CI 1.4-3.9) were associated with incidence of CTR. DISCUSSION: CTR is a common surgical procedure, performed on 1.9% of men and 4.1% of women during their lifetimes. Obesity and hand osteoarthritis are associated with an increased risk of CTR. Muscle Nerve 58: 497-502, 2018.

A screening tool for the risk of disability retirement due to musculoskeletal disorders.

Objective This study aimed to develop and validate a risk screening tool using a points system to assess the risk of future disability retirement due to musculoskeletal disorders (MSD). Methods The development population, the Health 2000 Survey, consisted of a nationally representative sample of Finnish employees aged 30-60 years (N=3676) and the validation population, the Helsinki Health Study, consisted of employees of the City of Helsinki aged 40-60 years (N=6391). Both surveys were linked to data on disability retirement awards due to MSD from national register for an 11-year follow-up. Results The discriminative ability of the model with seven predictors was good (Gönen and Heller's K concordance statistic=0.821). We gave points to seven predictors: sex-dependent age, level of education, pain limiting daily activities, multisite musculoskeletal pain, history of arthritis, and surgery for a spinal disorder or carpal tunnel syndrome. A score of 3 or higher out of 7 (top 30% of the index) had good sensitivity (83%) and specificity (70%). Individuals at the top 30% of the risk index were at 29 [95% confidence interval (CI) 15-55) times higher risk of disability retirement due to MSD than those at the bottom 40%. Conclusion This easy-to-use screening tool based on self-reported risk factor profiles can help identify individuals at high risk for disability retirement due to MSD.

Risk factors for first hospitalization due to meniscal lesions - a population-based cohort study with 30 years of follow-up.

BACKGROUND: Meniscal lesions are among the most common injuries of the knee, yet limited epidemiologic data is available on their risk factors. We investigated the association of lifestyle factors and physical strenuousness of work on knee injuries with a focus on meniscal lesions. METHODS: We examined a nationally representative sample of persons aged 30 to 59 years, who participated in a comprehensive health examination (the Mini-Finland Health Survey). Subjects without any injury or osteoarthritis in the knee joint at baseline (n = 4713) were subsequently followed via the National Hospital Discharge Register up to 30 years. RESULTS: During the follow-up, 338 knee injuries were identified of which 224 were meniscal lesions. Obesity and regular leisure time physical exercise were associated with an increased risk of first hospitalization due to meniscal lesions (hazard ratio (HR) 1.62 and 95% confidence interval (CI) 1.06-2.48 and 1.53, 95% CI 1.05-2.23, respectively). The types of sports predicting the highest risk of meniscal lesions were ballgames, gymnastics and jogging. Physical strenuousness of work did not predict meniscal lesion. The hazard of other knee injury was increased among those reporting irregular or regular physical exercise at baseline (HR 1.64, 95% CI 1.03-2.64 and 1.88 CI 1.05-2.36, respectively). Smoking or alcohol intake were not associated with knee injuries. CONCLUSIONS: Better safety measures in high-risk sports and weight control would likely improve the prevention of meniscal lesions in populations.

International Differences in the Risk of Death from Smoking and Obesity: The Case of the United States and Finland.

Despite much interest in the health risks associated with behavioral factors, little is known about whether individuals residing in different countries experience a different set of risks. International comparisons of the death risks from major behavioral factors can shed light on whether features of health systems and epidemiological histories modify the health effects of risky behaviors. We used nationally representative samples and mortality linkages spanning the 1971-2014 period from the United States and Finland to examine cross-national differences in the risks of death from cigarette smoking and obesity. We evaluated both current and former smoking and current and prior obesity. In 1990, the approximate midpoint of our study, the death risks from current smoking were about 55% higher in U.S. women compared to Finnish women, but similar for men in the two countries. Death risks from smoking significantly increased over the period for women in both countries and there was no parallel increase in risks among men. Death risks from obesity did not significantly differ in the two countries and no significant trend in the risks were detected in either country. Reasons for the relatively high and increasing risks from smoking among American women warrant further evaluation.

Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies.

BACKGROUND: The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica. METHODS: We included 4 Finnish prospective cohort studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital discharge register data. We conducted a random-effects individual participant data meta-analysis. RESULTS: After adjustment for confounding factors, current smoking at baseline increased the risk of subsequent hospitalization for sciatica by 33% (95% confidence interval [CI], 13%-56%), whereas past smokers were no longer at increased risk. Obesity defined by body mass index increased the risk of hospitalization for sciatica by 36% (95% CI 7%-74%), and abdominal obesity defined by waist circumference increased the risk by 41% (95% CI 3%-93%). Walking or cycling to work reduced the risk of hospitalization for sciatica by 33% (95% CI 4%-53%), and the effect was independent of body weight and other leisure activities, while other types of leisure activities did not have a statistically significant effect. CONCLUSIONS: Smoking and obesity increase the risk of hospitalization for sciatica, whereas walking or cycling to work protects against hospitalization for sciatica. Walking and cycling can be recommended for the prevention of sciatica in the general population.

Tuberculosis, Airway Obstruction and Mortality in a Finnish Population.

There is little long-term follow-up data concerning the association between past pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to analyse a national health examination survey data from 6701 adult Finns undergoing spirometry between 1978 and 1980 (follow-up through 2013). We identified TB either through a disease history or by a TB-indicative scar on a chest x-ray. We specified obstruction using the lower limit of normal (LLN) and classified severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4. After adjusting for smoking and other confounders, past TB associated with obstruction. Compared to non-TB patients, the adjusted odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52-3.21) among patients with a scar recorded by one radiologist, 2.48 (1.63-3.78) when recorded by both radiologists and 4.59 (2.86-7.37) among patients with a disease history. Among those with neither past TB nor obstruction, with past TB only, with an obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for subsequent mortality of 1.00 (reference), 1.11 (1.03-1.20), 1.62 (1.31-2.00) and 1.77 (1.45-2.16), adjusted for age, gender, smoking, body mass index (BMI), physical activity, education and general health. In conclusion, past TB strongly determines obstruction, although on its own quite weakly predicts premature death. TB and obstruction combined predict an additive mortality pattern.

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.

BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.

Genome-wide association studies (GWAS) of complex behavioural phenotypes such as cigarette smoking typically employ self-report phenotypes. However, precise biomarker phenotypes may afford greater statistical power and identify novel variants. Here we report the results of a GWAS meta-analysis of levels of cotinine, the primary metabolite of nicotine, in 4,548 daily smokers of European ancestry. We identified a locus close to UGT2B10 at 4q13.2 (minimum p = 5.89 × 10(-10) for rs114612145), which was consequently replicated. This variant is in high linkage disequilibrium with a known functional variant in the UGT2B10 gene which is associated with reduced nicotine and cotinine glucuronidation activity, but intriguingly is not associated with nicotine intake. Additionally, we observed association between multiple variants within the 15q25.1 region and cotinine levels, all located within the CHRNA5-A3-B4 gene cluster or adjacent genes, consistent with previous much larger GWAS using self-report measures of smoking quantity. These results clearly illustrate the increase in power afforded by using precise biomarker measures in GWAS. Perhaps more importantly however, they also highlight that biomarkers do not always mark the phenotype of interest. The use of metabolite data as a proxy for environmental exposures should be carefully considered in the context of individual differences in metabolic pathways.

Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies.

BACKGROUND: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. OBJECTIVE: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors. DESIGN: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets. RESULTS: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk. CONCLUSIONS: Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.

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.