Fredrik Nyberg

Lung cancer and cigarette smoking in Europe: An update of risk estimates and an assessment of inter-country heterogeneity

Ten case‐control studies have been carried out in 6 European countries to investigate the major risk factors for lung cancer. Carcinogenic effect from cigarette smoke was the most relevant interest in our study, which has included 7,609 cases of lung cancer and 10,431 controls, mainly population based. The results indicate elevated odds ratios (ORs; 23.9 among men and 8.7 among women) with attributable risks exceeding 90% for men and close to 60% for women. A large, and statistically significant, variability of the results across countries was detected after adjusting for the most common confounding variables, and after controlling, at least in part, for the instability of the ORs due to the small number of non‐smokers in some of the study subsets. This pattern of lung cancer risk associated with cigarettes smoke, across different European regions, reflects inherent characteristics of the studies as well as differences in smoking habits, particularly calender periods of starting, and it is likely to have been influenced by effect modifiers like indoor radon exposure, occupation, air pollution and dietary habits.

Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction: the HEAPSS study

Background: Acute myocardial infarction (AMI) is the leading cause of death attributed to cardiovascular diseases. An association between traffic related air pollution and AMI has been suggested, but the evidence is still limited. Objectives: To evaluate in a multicentre study association between hospitalisation for first AMI and daily levels of traffic related air pollution. Methods: The authors collected data on first AMI hospitalisations in five European cities. AMI registers were available in Augsburg and Barcelona; hospital discharge registers (HDRs) were used in Helsinki, Rome and Stockholm. NO2, CO, PM10 (particles <10 μm), and O3 were measured at central monitoring sites. Particle number concentration (PNC), a proxy for ultrafine particles (<0.1 μm), was measured for a year in each centre, and then modelled retrospectively for the whole study period. Generalised additive models were used for statistical analyses. Age and 28 day fatality and season were considered as potential effect modifiers in the three HDR centres. Results: Nearly 27 000 cases of first AMI were recorded. There was a suggestion of an association of the same day CO and PNC levels with AMI: RR = 1.005 (95% CI 1.000 to 1.010) per 0.2 mg/m3 and RR = 1.005 (95% CI 0.996 to 1.015) per 10000 particles/cm3, respectively. However, associations were only observed in the three cities with HDR, where power for city-specific analyses was higher. The authors observed in these cities the most consistent associations among fatal cases aged <75 years: RR at 1 day lag for CO = 1.021 (95% CI 1.000 to 1.048) per 0.2 mg/m3, for PNC = 1.058 (95% CI 1.012 to 1.107) per 10000 particles/cm3, and for NO2 = 1.032 (95% CI 0.998 to 1.066) per 8 μg/m3. Effects of air pollution were more pronounced during the warm than the cold season. Conclusions: The authors found support for the hypothesis that exposure to traffic related air pollution increases the risk of AMI. Most consistent associations were observed among fatal cases aged <75 years and in the warm season.

A multicenter case-control study of diet and lung cancer among non-smokers

Objective: We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case–control study.Methods: 506 non-smoking incident lung cancer cases were identified in the eight centers along with 1045 non-smoking controls. Dietary habits were assessed using a quantitative food-frequency questionnaire administered by personal interview. Based on this information, measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated.Results: Protective effects against lung cancer were observed for high consumption of tomatoes, (odds ratio (OR) = 0.5; 95% confidence interval (CI) 0.4–0.6), lettuce (OR = 0.6; 95% CI 0.3–1.2), carrots (OR = 0.8; 95% CI 0.5–1.1), margarine (OR = 0.7; 95% CI 0.5–0.8) and cheese (OR = 0.7; 95% CI 0.5–1.0). Only weak protective effects were observed for high consumption of all carotenoids (OR = 0.8; 95% CI 0.6–1.0), beta-carotene (OR=0.8; 95% CI 0.6–1.1) and retinol (OR = 0.9; 95% CI 0.7–1.1). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7; 95% CI 0.4–1.2) and small cell carcinoma (OR = 0.7; 95% CI 0.4–1.2), and were not apparent for adenocarcinoma (OR = 0.9; 95% CI 0.6–1.3). Similarly, any excess risk associated with meat, butter and egg consumption was restricted to squamous and small cell carcinomas, but was not detected for adenocarcinomas.Conclusions: This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25%, and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.

Aerosol Particle Number Concentration Measurements in Five European Cities Using TSI-3022 Condensation Particle Counter over a Three-Year Period during Health Effects of Air Pollution on Susceptible Subpopulations

Abstract In this study, long-term aerosol particle total number concentration measurements in five metropolitan areas across Europe are presented. The measurements have been carried out in Augsburg, Barcelona, Helsinki, Rome, and Stockholm using the same instrument, a condensation particle counter (TSI model 3022). The results show that in all of the studied cities, the winter concentrations are higher than the summer concentrations. In Helsinki and in Stockholm, winter concentrations are higher by a factor of two and in Augsburg almost by a factor of three compared with summer months. The winter maximum of the monthly average concentrations in these cities is between 10,000 cm-3 and 20,000 cm-3, whereas the summer min is ˜;5000–6000 cm-3. In Rome and in Barcelona, the winters are more polluted compared with summers by as much as a factor of 4–10. The winter maximum in both Rome and Barcelona is close to 100,000 cm-3, whereas the summer minimum is >10,000 cm-3. During the weekdays the maximum of the hourly average concentrations in all of the cities is detected during the morning hours between 7 and 10 a.m. The evening maxima were present in Barcelona, Rome, and Augsburg, but these were not as pronounced as the morning ones. The daily maxima in Helsinki and Stockholm are close or even lower than the daily minima in the more polluted cities. The concentrations between these two groups of cities are different with a factor of about five during the whole day. The study pointed out the influence of the selection of the measurement site and the configuration of the sampling line on the observed concentrations.

Dietary factors and risk of lung cancer in never-smokers

We studied dietary risk factors for lung cancer among never‐smokers in a population‐based case–control study in Stockholm, 1989–1995. Study subjects were older than 30 years of age and had never smoked regularly. A total of 124 cases (35 men, 89 women) and 235 controls (72 men, 163 women) participated. Exposure information was obtained at interview with study subjects. The never‐smoking status was validated by interviews with next‐of‐kin. A protective effect was suggested for vegetables, mediated primarily by carrots (relative risk [RR], 0.7; 95% confidence interval [CI], 0.4–1.3, and 0.6, 0.3–1.1 for intermediate and high consumption of carrots, respectively). Non‐citrus fruits appeared to lower the risk as well, with RR 0.6, 95% CI 0.3–1.3 and 0.5, 0.3–1.0 for intermediate and high consumption, respectively. A protective effect with dose‐response was also seen for intake of beta‐carotene and total carotenoids. Increased risks were seen for cultured milk products in both genders (RR 2.0, 95% CI 1.1–3.9 for intermediate and 1.6, 0.9–2.9 for high consumption), but for milk only among male high consumers. Our results support evidence linking a diet rich in vegetables and non‐citrus fruit with decreased lung cancer risk and suggests that among vegetables, carrot consumption is the most important component or marker for this effect in Sweden. The results regarding milk products could be consistent with dietary fat as a risk factor for lung cancer, although a more comprehensive assessment of fat intake is necessary to explore this relation. Int. J. Cancer 78:430–436, 1998.

Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample.

Background: Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Potential mechanisms include systemic inflammation and perturbation of the coagulation balance. Objectives: To investigate long- and short-term effects of air pollution exposure on serum levels of inflammatory (IL-6, TNF-α and CRP) and coagulation (fibrinogen and PAI-1) markers relevant for cardiovascular pathology. Methods: The study group consisted of a population sample of 1028 men and 508 women aged 45–70 years from Stockholm. Long-term air pollution exposure was assessed using spatial modelling of traffic-related NO2 and heating-related SO2 emissions at each subject’s residential addresses over retrospective periods of 1, 5 and 30 years. Short-term exposure was assessed as averages of rooftop measurements over 12–120 h before blood sampling. Results: Long-term exposures to both traffic-NO2 and heating-SO2 emissions showed consistent associations with IL-6 levels. 30-year average traffic-NO2 exposure was associated with a 64.5% (95% CI 6.7% to 153.8%) increase in serum IL-6 per 28.8 μg/m3 (corresponding to the difference between the 5th and 95th percentile exposure value), and 30-year exposure to heating-SO2 with a 67.6% (95% CI 7.1% to 162.2%) increase per 39.4 μg/m3 (5th–95th percentile value difference). The association appeared stronger in non-smokers, physically active people and hypertensive subjects. We observed positive non-significant associations of inflammatory markers with NO2 and PM10 during 24 h before blood sampling. Short-term exposure to O3 was associated with increased, and SO2 with decreased, fibrinogen levels. Conclusions: Our results suggest that exposure to moderate levels of air pollution may influence serum levels of inflammatory markers.

No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis : results from two Swedish population-based rheumatoid arthritis cohorts.

OBJECTIVE To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA. METHODS We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case-control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/MI/angina pectoris among patients with RA with that among population controls. RESULTS We could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9-1.1), the OR for MI was 1.0 (95% CI 0.9-1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9-1.2). CONCLUSION Shared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA-related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded.

Occupational risks for lung cancer among nonsmokers.

We conducted a case-control study in 12 European study centers to evaluate the role of occupational risk factors among nonsmokers. We obtained detailed occupational histories from 650 nonsmoking cases (509 females/141 males) and 1,542 nonsmoking controls (1,011 females/531 males). On the basis of an a priori definition of occupations and industries that are known (list A) or suspected (list B) to be associated with lung carcinogenesis, we calculated odds ratios (ORs) for these occupations, using unconditional logistic regression models and adjusting for sex, age, and center effects. Among nonsmoking men, an excess relative risk was observed among those who had worked in list-A occupations [OR = 1.52; 95% confidence interval (CI) = 0.78–2.97] but not in list-B occupations (OR = 1.05; 95% CI = 0.60–1.83). Among nonsmoking women, there was an elevation of risk for list-A occupations (OR = 1.50; 95% CI = 0.49–4.53), although this estimate was imprecise, given that less than 1% of cases and controls were exposed. Exposure to list-B occupations was associated with an increase in relative risk (OR = 1.69; 95% CI = 1.09–2.63) in females, but not in males. Women who had been laundry workers or dry cleaners had an OR of 1.83 (95% CI = 0.98–3.40). Our findings confirm that certain occupational exposures are associated with an increased risk for lung cancer among both female and male nonsmokers; however, knowledge on occupational lung carcinogens is biased toward agents to which mainly men are exposed.

A European validation study of smoking and environmental tobacco smoke exposure in nonsmoking lung cancer cases and controls

Objectives: The purpose of this study was to validate, in a case-control study, the reporting by lung cancer cases and controls of their own lifetime smoking habits and of the smoking habit of the spouse. Methods: In a multicenter (Sweden, Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung cancer, subjects were screened by repeated probing to exclude regular smokers of one cigarette/day or more for one year or more, and to quantify any occasional smoking. We then performed a short validation interview with next-of-kin in three centers. Results: Only five of 408 index subjects who had never smoked regularly (1.7 percent) were reported by next-of-kin to be former regular smokers. These subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack years. Among 351 subjects with quantitative smoking information from both sources who reported ever smoking 400 cigarettes or less (the definition of never-smoker used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more than this amount occasionally according to next-of-kin. Misclassification was not higher for cases than controls. Relative risks for lung cancer associated with indicators of ETS exposure were not substantially altered by excluding the nine possibly misclassified subjects. The reports from 223 pairs of index subjects and next-of kin regarding the cumulative amount smoked by the spouse agreed quite well (Spearmans rank correlation 0.75 for reported smokers, 0.92 for all subjects). Only one index subject failed to report a spouse who had smoked regularly (99 percent sensitivity). Conclusions: Smoking status and exposure to spousal ETS as reported by lung cancer cases and controls agreed strongly with reports by next-of-kin. Overall, our results suggest that bias from smoker misclassification is likely to be insignificant, and they contribute to the evidence linking exposure to ETS with an increased risk of lung cancer.

Exposure to environmental tobacco smoke and risk of adenocarcinoma of the lung

We conducted a case‐control study of adenocarcinoma of the lung and exposure to environmental tobacco smoke (ETS) in 7 countries. We interviewed 70 cases of adenocarcinoma of the lung and 178 population or hospital controls. All subjects had smoked fewer than 400 cigarettes in their lifetimes. Ever exposure to ETS from the parents during childhood was associated with a decreased risk [odds ratio (OR) 0.6, 95% confidence interval (CI) 0.3–1.2], and there was a suggestion of a decreasing trend in risk with increasing duration of exposure. Ever exposure to ETS from the spouse was not associated with an increased risk (OR 1.0, 95% CI 0.5–1.8), while the OR of ever exposure to ETS at the workplace was 1.5 (95% CI 0.8–3.0). For both exposure sources, an increased risk was observed among the highly exposed, and the OR among those with the highest duration of exposure to ETS from the spouse or at the workplace was 1.8 (95% CI 0.5–6.2). A similar risk was estimated for current exposure to ETS from either source. Our results confirm previous reports of a weak effect of adult ETS exposure on risk of adenocarcinoma of the lung. Bias and confounding cannot be excluded as explanations for the apparent decrease in risk from childhood exposure. Int. J. Cancer 83:635–639, 1999.