Ann Olsson

Cigarette smoking and lung cancer – relative risk estimates for the major histological types from a pooled analysis of case-control studies

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age‐adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8–143.2) for SqCC, 111.3 (95% CI: 69.8–177.5) for SCLC and 21.9 (95% CI: 16.6–29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5–124.6), 108.6 (95% CI: 50.7–232.8) and 16.8 (95% CI: 9.2–30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.

Exposure to Diesel Motor Exhaust and Lung Cancer Risk in a Pooled Analysis from Case-Control Studies in Europe and Canada

RATIONALE Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships. OBJECTIVES Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders. METHODS The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure. MEASUREMENTS AND MAIN RESULTS Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant. CONCLUSIONS Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.

Tears in the vagina, perineum, sphincter ani, and rectum and first sexual intercourse after childbirth: a nationwide follow-up.

BACKGROUND The first sexual intercourse after childbirth may be challenging for women, especially if the birth resulted in injuries in the genital area. The purpose of this study was to investigate whether or not tears in the vagina, perineum, sphincter ani, or rectum hindered sexual intercourse during the year after childbirth. METHODS We obtained information from 2,490 women in a population-based cohort identified at antenatal care. Information about first sexual intercourse was collected by means of a questionnaire sent 1 year after birth to the women and about womens tears reported in the population-based Swedish Medical Birth Register. RESULTS Adjusted relative risks with 95 percent confidence intervals for not having had sexual intercourse within 3 and 6 months, respectively, after childbirth were 1.5 (95% CI 1.2-1.8) and 1.6 (95% CI 1.2-2.3) for tears in the vagina, 1.4 (95% CI 1.1-1.6) and 1.5 (95% CI 1.1-2.1) for tears in the perineum, and 2.1 (95% CI 1.4-3.1) and 2.2 (95% CI 1.1-4.6) for tears in the sphincter ani and rectum. No statistically significant differences were found at 1-year follow-up. No associations between episiotomy and delay in resuming intercourse were found after adjusting the relative risks. CONCLUSIONS Tears in the vagina, perineum, sphincter ani, or rectum are associated with a delay in womens resumption of sexual intercourse 6 months after childbirth in Sweden.

Occupational exposure to polycyclic aromatic hydrocarbons and lung cancer risk: a multicenter study in Europe.

Background Lung cancer incidence in Central and Eastern Europe (CEE) is among the highest in the world, and the role of occupational exposures has not been adequately studied in these countries. Objectives To investigate the contribution of occupational exposure to polycyclic aromatic hydrocarbons (PAH) to lung cancer in CEE. Methods A case–control study was conducted in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, as well as the United Kingdom (UK) between 1998 and 2002. Occupational and socio-demographic information was collected through interviews from 2861 newly diagnosed lung cancer cases and 2936 population or hospital controls. Industrial hygiene experts in each country evaluated exposure to 70 occupational agents, whereof 15 mixtures containing PAH. ORs of lung cancer were calculated after adjusting for other occupational exposures and tobacco smoking. Results The OR for ever exposure to PAH in the CEE countries was 0.93 (95% CI 0.77 to 1.14). The ORs for the highest category of cumulative exposure, duration of exposure and intensity of exposure were 1.13 (95% CI 0.80 to 1.58), 1.02 (95% CI 0.66 to 1.57) and 1.11 (95% CI 0.60 to 2.05), respectively. The OR for ever PAH exposure in the UK was 1.97 (95% CI 1.16 to 3.35). Conclusion Occupational PAH exposure does not appear to substantially contribute to the burden of lung cancer in CEE. The apparently stronger effect observed in the UK may be due to high exposure levels and a joint effect with asbestos.

A case-control study of lung cancer nested in a cohort of European asphalt workers.

Background We conducted a nested case–control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed. Objective We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers. Methods Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002–2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar. Results A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84–1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88–1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate. Conclusions We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.

Development of an Exposure Measurement Database on Five Lung Carcinogens (ExpoSYN) for Quantitative Retrospective Occupational Exposure Assessment

BACKGROUND SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. METHODS Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. RESULTS The ExpoSYN database currently includes 356 551 measurements from 19 countries. In total, 140 666 personal and 215 885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). CONCLUSIONS ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies.

Occupational exposure to organic dust increases lung cancer risk in the general population

Background Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population. Methods The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case–control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. Results Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products. Conclusion Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case–control study.

Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicentre case-control study in Europe.

Objectives: To investigate the contribution of occupational exposure to asbestos and man-made vitreous fibres (MMVF) to lung cancer in high-risk populations in Europe. Methods: A multicentre case-control study was conducted in six Central and Eastern European countries and the UK, during the period 1998–2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking. Results: The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found. Conclusion: In this large community-based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.

Modelling of occupational respirable crystalline silica exposure for quantitative exposure assessment in community-based case-control studies

We describe an empirical model for exposure to respirable crystalline silica (RCS) to create a quantitative job-exposure matrix (JEM) for community-based studies. Personal measurements of exposure to RCS from Europe and Canada were obtained for exposure modelling. A mixed-effects model was elaborated, with region/country and job titles as random effect terms. The fixed effect terms included year of measurement, measurement strategy (representative or worst-case), sampling duration (minutes) and a priori exposure intensity rating for each job from an independently developed JEM (none, low, high). 23,640 personal RCS exposure measurements, covering a time period from 1976 to 2009, were available for modelling. The model indicated an overall downward time trend in RCS exposure levels of -6% per year. Exposure levels were higher in the UK and Canada, and lower in Northern Europe and Germany. Worst-case sampling was associated with higher reported exposure levels and an increase in sampling duration was associated with lower reported exposure levels. Highest predicted RCS exposure levels in the reference year (1998) were for chimney bricklayers (geometric mean 0.11 mg m(-3)), monument carvers and other stone cutters and carvers (0.10 mg m(-3)). The resulting model enables us to predict time-, job-, and region/country-specific exposure levels of RCS. These predictions will be used in the SYNERGY study, an ongoing pooled multinational community-based case-control study on lung cancer.

Effect Modification of the Association of Cumulative Exposure and Cancer Risk by Intensity of Exposure and Time Since Exposure Cessation: A Flexible Method Applied to Cigarette Smoking and Lung Cancer in the SYNERGY Study

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.