Phytoestrogen intake and other dietary risk factors for low motile sperm count and poor sperm morphology.

BACKGROUND: Few potentially modifiable risk factors of male infertility have been identified, and while different diets and food groups have been associated with male infertility, evidence linking dietary factors including phytoestrogens and semen quality is limited and contradictory. OBJECTIVES: To study the associations between phytoestrogen intake and other dietary factors and semen quality. MATERIALS AND METHODS: A case-referent study was undertaken of the male partners, of couples attempting conception with unprotected intercourse for 12 months or more without success, recruited from 14 UK assisted reproduction clinics. A total of 1907 participants completed occupational, lifestyle and dietary questionnaires before semen quality (concentration, motility and morphology) were assessed. Food intake was estimated by a 65-item food frequency questionnaire (FFQ) covering the 12 months prior to recruitment. Analyses of dietary risk factors for low motile sperm concentration (MSC: <4.8 × 106 /mL) and poor sperm morphology (PM: <4% normal morphology) used unconditional logistic regression, accounting for clustering of subjects within the clinics, first without, and then with, adjustment for confounders associated with that outcome. RESULTS: High consumption of daidzein (≥13.74 µg/d), a phytoestrogen found in soy products, was a protective factor for MSC with an odds ratio (95%CI) of 0.58 (0.42-0.82) after adjustment for clustering and potential confounding. Dietary risk factors for PM after similar adjustment showed that drinking whole milk (OR 0.67, 95%CI 0.47-0.96) and eating red meat were protective with an OR 0.67 (0.46-0.99) for eating red meat >3 times/wk. DISCUSSION: In this case-referent study of men attending an infertility clinic for fertility diagnosis, we have identified that low MSC is inversely associated with daidzein intake. In contrast, daidzein intake was not associated with PM but eating red milk and drinking whole milk were protective. CONCLUSIONS: Dietary factors associated with semen quality were identified, suggesting that male fertility might be improved by dietary changes.

Urinary metal concentrations among female welders.

As part of a Canada-wide study of women entering non-traditional trades [Women's Health in Apprenticeship Trades-Metalworkers and Electricians (WHAT-ME)], we examined spot urine samples from women welders in Alberta to determine whether urinary metal concentrations exceeded those of the general population, to compare levels to previously published urinary concentrations in male welders and to examine the relationship with welding tasks. Women mailed-in urine samples collected close to the time of completing a detailed exposure questionnaire, including welding tasks on their most recent day welding at work. Of 53 welders working in their trade, 45 had urinary creatinine >0.3-≤3.0g l(-1) and were included in analyses. Seven metals were examined for which both population and male welder urinary concentrations were available: cadmium, chromium, cobalt, copper, manganese, nickel, and zinc. Principal component analysis was used to extract three components from natural log transformed creatinine-corrected metal concentrations. Of the 45 women, 17 reported more than one main task. Overall two thirds worked in fabrication, a third on pipe welding, and smaller numbers on repair, in construction or other tasks: manual metal arc welding was reported by 62%, semi-automatic arc welding by 47%, and arc welding with a tungsten electrode by 15%. In multiple regression analyses, little relation was found between urinary metals and task or type of welding, except for cadmium where lower levels were seen in those reporting semi-automatic manual welding (after adjustment for age and smoking). The proportion of women welders exceeding the selected general population 95th percentile was high for manganese (96%) and chromium (29%). Urinary metal concentrations were similar to those reported for male welders with only manganese, with a geometric mean in women of 1.91 µg g(-1) creatinine, and perhaps copper (11.8 µg g(-1) creatinine), consistently lower in male welders. Although not evident from the task analysis reported here, differences in exposure by sex may be explained by type of welding or by other work practices. A closely comparable cohort of male welders would be necessary to examine this hypothesis more fully.

Maternal exposure to bisphenol-A and fetal growth restriction: a case-referent study.

We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns <10 percentile of expected weight for gestational age and sex were individually matched on sex, maternal smoking and maternal age to referents with weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was estimated from maternal serum collected at 15-16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard deviations (2.3-2.5). Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons.

Paid work, domestic work, and other determinants of pregnancy outcome in Ibadan, southwest Nigeria.

OBJECTIVE: To identify the determinants of low birth weight (LBW), preterm birth, and stillbirth, and the factors associated with paid or domestic work that affected pregnancy outcome in Ibadan, Nigeria. METHODS: A cross-sectional study of women who delivered live or stillborn singleton neonates at 4 hospitals between February and June 2008. Participants were interviewed to obtain information on paid and domestic work activities during pregnancy, as well as obstetric history. Pregnancy outcomes and other clinical data were extracted from case notes. RESULTS: A total of 1504 mothers aged 20-45 years recorded 137 (9.1%) LBW neonates (<2.5 kg), 154 (10.2%) preterm deliveries (<37 weeks), and 56 (3.7%) stillbirths. There was no overall increased risk of these outcomes among working mothers. Multivariate logistic regression analysis of working mothers who had booked their deliveries revealed that lifting heavy objects at home, a clinical record of proteinuria, and hospital admission during pregnancy were associated with LBW. Predictors for preterm birth were self-reported exposure to vibration at work, nulliparity, history of preterm birth, 4 or fewer compared with more than 8 antenatal visits, and prolonged rupture of membranes. Predictors for stillbirth were low education and prolonged rupture of membranes. CONCLUSION: The results further support recommendations that physical exertion in paid and domestic work should be reduced during pregnancy.

Second WCB claims: who is at risk?

OBJECTIVES: Many workers with one Workers' Compensation Board (WCB) claim make further claims. If the characteristics of the job, initial injury or worker were predictive of an early second claim, interventions at the time of return to work after the first claim might be effective in reducing the burden of work-related injury. This report explores the characteristic of those who make a second claim. METHODS: Records of all Alberta WCB claims from January 1, 1995, to December 31, 2004, for individuals 18 to < 66 years old were reviewed. For each individual's first claim, sex and age of claimant, type of injury, type of accident, occupation, industry, an indicator of company size, and industry claim rate were extracted, as well as the date of any second claim. The likelihood of second claim and mean time to second claim were estimated. Multivariate analyses were performed using Cox regression. RESULTS: 1,047,828 claims were identified from 490,230 individuals. Of these, 49.2% had at least two claims. In the multivariate model a reduced time to second claim was associated with male sex, younger age and some types of injury and accident. Machining trades were at highest risk of early second claim (hazard ratio [HR] 2.54 compared with administration), and of the industry sectors manufacturing was at highest risk (HR 1.37 compared with business, personal and professional services). CONCLUSION: Some caution is needed in interpreting these data as they may be affected by under-reporting and job changes between claims. Nonetheless, they suggest that there remains room for interventions to reduce the considerable differences in risk of a second claim among workers, jobs and industries.

Substance use of pregnant women and early neonatal morbidity: where to focus intervention?

BACKGROUND: Few studies, and none in Canada, have examined the relation between maternal smoking, alcohol consumption and drug dependence during pregnancy and early neonatal morbidity. METHODS: We analyzed records of singleton live births in Alberta, Canada. Markers of neonatal morbidity were Apgar scores (< 7 at 5 minutes postpartum) and resuscitation measures (2001-2005, N = 191,686), and neonatal intensive care unit (NICU) admissions (2002-2005, N = 154,924). Logistic regression was used to estimate odds ratios (ORs) for self-reported substance use and maternal health before conception, adjusting for maternal age, parity, year and fetal gender. Univariate ORs and population-attributable fractions were computed with and without correction for under-reporting of substance use. RESULTS: Maternal smoking during pregnancy was the most prevalent risk factor, affecting 20% of mothers by self-report, with the figure being possibly twice as high once corrected for under-reporting. Smoking (ORs 1.2), alcohol consumption (ORs 1.2-1.5) and drug dependence (ORs 1.7-2) by the mother during pregnancy were associated with increased risk for each of the markers of early neonatal morbidity (p < 0.05, after correcting for covariates). Eliminating the most common among these risk factors, maternal smoking, would prevent 10-15% of each of the three neonatal morbidity markers. Other recorded factors related to mother's pre-conception health, despite some strong associations, were responsible for only a small proportion of cases. DISCUSSION: We conclude that in preventing early neonatal morbidity among singleton births in Alberta, control of maternal smoking, the most common of the potentially modifiable risk factors, remains an important goal.

Maternal exposure to perfluorinated acids and fetal growth.

The widespread detection of perfluorinated acids (PFAs) in humans and known developmental toxicity in animals has raised concern about their potential effects on human reproductive health. Our objective was to determine whether increasing maternal exposure to PFAs is associated with adverse effects on fetal growth and length of gestation in women giving birth in Alberta, Canada. We examined the concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) in a cohort of 252 pregnant women who gave birth to live singletons. Each of the women had undergone an early second trimester prenatal screen, and her serum was analyzed for PFA concentrations. Data on infant and maternal variables were collected from the delivery record completed at birth. Adjusted changes in birth weight per natural log (ng/ml) of PFOA (median 1.5 ng/ml), PFHxS (median 0.97 ng/ml), and PFOS (median 7.8 ng/ml) were -37.4 g (95% confidence interval (CI): -86.0 to 11.2 g), 21.9 g (-23.4 to 67.2 g), and 31.3 g (-43.3 to 105.9 g), respectively. Mean birth weight z-score, standardized for gestational age and gender, length of gestation, and risk of preterm birth did not appear to be influenced by maternal PFA exposure. When PFA concentrations were divided into tertiles, similar patterns were observed. These results suggest that maternal PFA exposure has no substantial effect on fetal weight and length of gestation at the concentrations observed in this population.

The impact of isolated maternal hypothyroxinemia on perinatal morbidity.

OBJECTIVE: To determine whether maternal hypothyroxinemia during early pregnancy is associated with adverse perinatal outcomes. METHODS: Serum samples of a prospective cohort of 879 women collected at 15-16 weeks of pregnancy were analyzed for thyroid-stimulating hormone (TSH) and free thyroxine (T4) concentrations. Women with TSH levels within the normal reference range (0.15-4.0 mU/L) and free T4 levels below the 10th percentile of the sample (8.5 pmol/L) were classified as hypothyroxinemic and were compared with euthyroid women (who had normal TSH and free T4 levels). Thyroid hormone measures were linked to pregnancy outcomes, including small for gestational age (SGA), standardized birth weight z-score, preterm delivery, and Apgar score used as a measure of early neonatal morbidity. RESULTS: Among 89 hypothyroxinemic women, there was no evidence of an increased risk for fetal growth restriction, preterm birth, or low Apgar score. The relative risk of delivering an SGA infant was 0.38 (95% CI 0.11 to 1.33), the mean difference in birth weight z-score was 0.035 (95% CI -0.17 to 0.24), and the risk of preterm delivery was 0.79 (95% CI 0.38 to 1.67). None of the hypothyroxinemic women gave birth to an infant with a five-minute Apgar score <7. When free T4 levels were substituted for categories of thyroid hormone function, the pattern of results remained unaltered. CONCLUSION: Isolated maternal hypothyroxinemia was not observed to have any adverse effect on fetal growth or pregnancy outcome. This study does not provide evidence to support treatment of this condition to prevent fetal growth restriction or neonatal morbidity.

Relative performance of different exposure modeling approaches for sulfur dioxide concentrations in the air in rural western Canada.

BACKGROUND: The main objective of this paper is to compare different methods for predicting the levels of SO2 air pollution in oil and gas producing area of rural western Canada. Month-long average air quality measurements were collected over a two-year period (2001-2002) at multiple locations, with some side-by-side measurements, and repeated time-series at selected locations. METHODS: We explored how accurately location-specific mean concentrations of SO2 can be predicted for 2002 at 666 locations with multiple measurements. Means of repeated measurements on the 666 locations in 2002 were used as the alloyed gold standard (AGS). First, we considered two approaches: one that uses one measurement from each location of interest; and the other that uses context data on proximity of monitoring sites to putative sources of emission in 2002. Second, we imagined that all of the previous year's (2001's) data were also available to exposure assessors: 9,464 measurements and their context (month, proximity to sources). Exposure prediction approaches we explored with the 2001 data included regression modeling using either mixed or fixed effects models. Third, we used Bayesian methods to combine single measurements from locations in 2002 (not used to calculate AGS) with different priors. RESULTS: The regression method that included both fixed and random effects for prediction (Best Linear Unbiased Predictor) had the best agreement with the AGS (Pearson correlation 0.77) and the smallest mean squared error (MSE: 0.03). The second best method in terms of correlation with AGS (0.74) and MSE (0.09) was the Bayesian method that uses normal mixture prior derived from predictions of the 2001 mixed effects applied in the 2002 context. CONCLUSION: It is likely that either collecting some measurements from the desired locations and time periods or predictions of a reasonable empirical mixed effects model perhaps is sufficient in most epidemiological applications. The method to be used in any specific investigation will depend on how much uncertainty can be tolerated in exposure assessment and how closely available data matches circumstances for which estimates/predictions are required.

Determinants of airborne concentrations of volatile organic compounds in rural areas of Western Canada.

We estimated the level and determinants of airborne concentrations of 26 volatile organic compounds (VOC) in rural Western Canada. A multisite, multimonth unbalanced two-factorial design was used to collect air samples at 1206 fixed sites across a geographic area associated with primary oil and gas industry in Alberta, northeastern British Columbia, and central and southern Saskatchewan from April 2001 to December 2002. Principal component factor analysis was used to group VOC into three mixtures. Factor I was a group of compounds dominated by benzene, toluene, ethyl-benzene, xylenes, and hexane. Factor II was mainly a group of vegetation-related monoterpenes and dichlorobenzenes. Factor III was a group of chlorinated VOC. Linear mixed effects models were applied to identify the determinants of airborne concentrations of VOC and evaluate the association between these factors and oil and gas facilities. Our results indicated that the studied VOC were present in small (ng/m3) quantities. Components of Factor I VOC showed a seasonal variation with maxima in winter and minima in summer, whereas components of Factor II displayed an opposite seasonal trend. Components of Factor III did not show a clear seasonal pattern. We observed that oil and gas facilities only contribute to airborne concentrations of components of Factor I. Proximity to batteries (within 2 km) was most influential in determining monthly airborne concentrations of components of Factor I, followed by gas and oil wells. Modification of batteries to reduce evaporation and leakage might be considered as a measure to control airborne concentrations of compounds such as benzene and toluene.

Industrial sources influence air concentrations of hydrogen sulfide and sulfur dioxide in rural areas of western Canada.

A survey of monthly average concentrations of sulfur dioxide (SO2) and hydrogen sulfide (H2S) at rural locations in western Canada (provinces of Alberta, British Columbia, and Saskatchewan) was conducted in 2001-2002, as part of an epidemiological study of the effects of oil and gas industry emissions on the health of cattle. Repeated measurements were obtained at some months and locations. We aimed to develop statistical models of the effect of oil and gas infrastructure on air concentrations. The regulatory authorities supplied the information on location of the different oil and gas facilities during the study period and, for Alberta, provided data on H2S content of wells and flaring volumes. Linear mixed effects models were used to relate observed concentrations to proximity and type of oil and gas infrastructure. Low concentrations were recorded; the monthly geometric mean was 0.1-0.2 ppb for H2S, and 0.3-1.3 ppb for SO2. Substantial variability between repeated measurements was observed. The precision of the measurement method was 0.005 ppb for both contaminants. There were seasonal trends in the concentrations, but the spatial variability was greater. This was explained, in part, by proximity to oil/gas/bitumen wells and (for SO2) gas plants. Wells within 2 km of monitoring stations had the greatest impact on measured concentrations. For H2S, 8% of between-location variability was explained by proximity to industrial sources of emissions; for SO2 this proportion was 18%. In Alberta, proximity to sour gas wells and flares was associated with elevated H2S concentrations; however, the estimate of the effect of sour gas wells in the immediate vicinity of monitoring stations was unstable. Our study was unable to control for all possible sources of the contaminants. However, the results suggest that oil and gas extraction activities contribute to air pollution in rural areas of western Canada.

Reported incidence and precipitating factors of work-related stress and mental ill-health in the United Kingdom (1996-2001).

BACKGROUND: Work-related mental ill-health appears to be increasing. Population-based data on incidence are scarce but in the United Kingdom occupational physicians and psychiatrists report these conditions to voluntary surveillance schemes. AIMS: To estimate the incidence of work-related stress and mental illness reported 1996-2001 by occupational physicians and 1999-2001 by psychiatrists. METHODS: Estimated annual average incidence rates were calculated by sex, occupation and industry against appropriate populations at risk. An in-house coding scheme was used to classify and analyse data on precipitating events. RESULTS: An estimated annual average of 3,624 new cases were reported by psychiatrists, and 2,718 by occupational physicians; the rates were higher for men in reports based on the former and for women on the latter. Most diagnoses were of anxiety/depression or work-related stress, with post-traumatic stress accounting for approximately 10% of cases reported by psychiatrists. High rates of ill-health were seen among professional and associated workers and in those in personal and protective services. Factors (such as work overload) intrinsic to the job and issues with interpersonal relations were the most common causes overall. CONCLUSIONS: The steep increase in new cases of work-related mental ill-health reported by occupational physicians since 1996 may reflect a greater willingness by workers to seek help but may also signify an increasing dissonance between workers' expectations and the work environment. Greater expertise is needed to improve the workplace by adjustment of job demands, improvement of working relations, increasing workers' capacities and management of organizational change.

Incidence by occupation and industry of work-related skin diseases in the United Kingdom, 1996-2001.

BACKGROUND: Work-related skin disease is common but few cases are documented in statutory reports or disability systems. Voluntary reporting by specialist physicians provides more complete information. AIMS: To summarize incidence rates of work-related skin diseases reported by consultant dermatologists and occupational physicians, with emphasis on contact and allergic dermatitis by occupation and industry. METHODS: Cases reported in 1996-2001 to the EPIDERM and OPRA national surveillance schemes were analysed by causal agent, occupation and industry, with incidence rates calculated against appropriate denominators. RESULTS: Average annual incidence rates based on data from dermatologists were 97 per million overall, 74 for contact dermatitis and 14 for neoplasia. The corresponding rates for occupational physicians were 623 overall, 510 and 2, respectively. For infective disease, the rates for occupational physicians were 28 compared to 2 for dermatologists. Contact dermatitis was most frequently attributed to rubber chemicals, soaps and cleaners, wet work, nickel and acrylics; most cases of contact urticaria were attributed to rubber chemicals or foods and flour. The pattern of incidence rates by occupation and industry was complex, but correlated with the probable type of exposure. Rates of contact dermatitis were highest among skilled workers in the petrochemical and rubber and plastic manufacturing industries, with machine operators and technical workers in metal and automotive industries also at increased risk. High proportions of cases attributed to rubber chemicals were in nurses and technicians in the health and social services. CONCLUSIONS: These findings identify jobs and types of work where contact with causal agents is common and potentially preventable.

Incidence and suspected cause of work-related musculoskeletal disorders, United Kingdom, 1996-2001.

BACKGROUND: Musculoskeletal conditions are the most common self-reported work-related disease, with high costs incurred from long-term disability. In the United Kingdom, occupational physicians and rheumatologists have been reporting new cases of work-related musculoskeletal disorders to voluntary surveillance schemes since 1996. AIMS: To estimate population incidence rates for work-related musculoskeletal disorders reported by rheumatologists and occupational physicians by occupation and industry, in relation to tasks and movements suspected as causal. METHODS: Estimated average annual incidence rates were calculated for nine main job categories and eight industrial groups; Labour Force Survey figures were used as the denominator for rheumatologists, and a special survey for the occupational physicians. These were then related to tasks and movements reported as causal. RESULTS: Between October 1997 and the end of 2001, an estimated 2,599 new cases/year were reported by rheumatologists, and from January 1996, 5,278 cases/year by occupational physicians. Average annual rates overall were 94 per million for rheumatologists and 1,643 per million for occupational physicians (a 17-fold difference). Jobs at highest risk for the upper limb were primarily clerical, craft-related and machine work. Tasks associated with upper limb disorders and with neck and back problems were predominantly keyboard work and heavy lifting, and in craft-related occupations with gripping or holding tools. CONCLUSIONS: Jobs at risk and the associate tasks were identified which should assist prevention, but the extent to which these factors were causal or aggravating previous injury requires further study. The much higher rates reported by occupational physicians reflect, in part, the type of industries they served.

Associations between smoking, GST genotypes and N7-methylguanine levels in DNA extracted from bronchial lavage cells.

N7-Methylguanine (N7-MeG) DNA adducts are markers of human exposure to methylating agents including tobacco-specific nitrosamines (TSNAs). Repair of this adduct is poor, so levels in lung tissue should reflect variation in both intensity of exposure and in metabolism. N7-MeG adducts in lung DNA from bronchial lavage samples were measured to determine whether levels were higher in smokers than non-smokers, and if levels were modified by genetic variation in carcinogen-metabolising enzymes. Adducts were detected in 38 out of 44 DNA samples by 32P post-labelling of the N7-methyldeoxyguanosine-3'-monophosphate (N7-MedGp) isolated from DNA digests by two-stage HPLC. N7-MeG adduct levels were higher in smokers than in never smokers ((9.99 +/-20.3)x10(-7) versus (0.58+/-0.50)x10(-7) N7-MedGp/deoxyguanosine-3'-monophosphate (dGp); P=0.02) and intermediate in ex-smokers ((5.59+/-15.6)x10(-7) N7-MedGp/dGp). Adduct levels tended to be higher in individuals with GSTM1 null, GSTT1 null or GSTP1 ile/ile genotypes. When genotypes were combined, N7-MedGp levels among GSTM1 null/GSTT1 null individuals (n=6) were higher than among those having at least one wild-type allele of these two genes ((26.1+/-38.0)x10(-7) versus (2.73+/-4.07)x10(-7) N7-MedGp/dGp), although the results were not statistically significant (P=0.13). Adduct levels were highest in individuals with three unfavourable genotypes (GSTM1 null/GSTT1 null and GSTP1 ile/ile) compared with others ((74.5+/-13.1)x10(-7) versus (2.64+/-3.89)x10(-7) N7-MedGp/dGp, P=0.02). N7-MeG adduct levels in DNA isolated from lung tissue thus reflect exposure to cigarette smoke, and genetic variation in carcinogen-metabolising enzymes may modify these levels.

Retrospective noise estimates for British nuclear workers using an alternative approach.

Exposure estimates were required to support an epidemiological study of occupational noise and cardiovascular disease. The study cohort consisted of male industrial workers employed at two nuclear facilities in England between 1945 and 1999 (n=2412). Historical noise exposure data were available from 6850 sound pressure measurements collected since 1965. Additional information was obtained from interviews with retired and long-term company personnel. Partly due to the lack of information provided by job title, coupled with the fact that noise behaves differently compared with chemical agents, an unusual approach was used to estimate noise exposure. Rather than grouping homogeneous exposure groups by job title or task, the assessors first used historical sampling data to estimate average area noise levels in each workplace where a survey had been performed. Noise contours were then estimated in the work area and, finally, individual estimates of exposure were further refined based on job title. Estimates were extrapolated to areas where noise surveys were not performed and adjustments were made for potential bias. Overall, noise exposure estimates ranged from 60 to 97 dBA, with a median of 86 dBA. For use in subsequent exposure-response analysis, cohort work histories were used to calculate exposure indices of cumulative, average intensity and exposure duration above 85 dBA. Validation exercises are discussed.

Cotinine levels and self-reported smoking status in patients attending a bronchoscopy clinic.

The reliability of self-reported smoking behaviour can vary and may result in bias if errors in misclassification vary with outcome. We examined whether self-report was an accurate measure of current smoking status in patients with malignant or non-malignant respiratory disease. Smoking behaviour was assessed by self-report and by analysis of whole blood for cotinine, a biomarker of exposure to cigarette smoke, in 166 patients attending a bronchoscopy clinic. Cotinine levels ranged from 2.5 to >400 ng ml(-1) blood and were higher in self-reported current smokers (173+/-123 ng ml(-1)) than in never smokers (3.7+/-8.7 ng ml(-1)) or ex-smokers (20.5+/-49.0 ng ml(-1)). Cotinine levels in self-reported current smokers increased with the numbers of cigarettes smoked (p=0.06), and levels in smokers and ex-smokers decreased with the reported length of time since the last cigarette (p=0.001). Using a cotinine level of 20 ng ml(-1) and self-report as the gold standard, the sensitivity and specificity for defining current smoking status were 90.2% and 82.4%, respectively. Out of a total of 125 self-reported current non-smokers, 23 (18.4%) had cotinine levels greater than 20 ng ml(-1). Smoking prevalence was significantly underestimated by self-report (24.7%) when compared with that defined using blood cotinine levels (36.1%: p<0.001). Misclassification of current smoking status was particularly high in ex-smokers, in patients without malignant respiratory disease, in men, and in those below the median age. Such differential misclassification may result in bias in studies examining associations between current smoking habits and disease risk.

GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk.

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients (n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients (n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29-0.87), particularly among men (OR 0.43, 95% CI 0.21-0.87) and those above the median age (OR 0.33, 95% CI 0.15-0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12-0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.