# Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer

Jan Hovanec, Jack Siemiatycki, David Conway, Ann Olsson, Pascal Guenel, Danièle Luce, Karl-Heinz Joeckel, Hermann Pohlabeln, Wolfgang Ahrens, Stefan Karrasch, et al.

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## To cite this version:

Jan Hovanec, Jack Siemiatycki, David Conway, Ann Olsson, Pascal Guenel, et al. Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer. Scandinavian Journal of Work, Environment and Health, 2021, 47 (6), pp.475-481. 10.5271/sjweh.3967. hal-03373102

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**Short communication**

Scand J Work Environ Health 2021;47(6):475-481

doi:10.5271/sjweh.3967

**Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer**

by Hovanec J, Siemiatycki J, Conway DI, Olsson A, Guenel P, Luce D, Jöckel K-H, Pohlabeln H, Ahrens W, Karrasch S, Wichmann H-E, Gustavsson P, Consonni D, Merletti F, Richiardi L, Simonato Lorenzo, Fortes C, Parent M-É, McLaughlin JR, Demers P, Landi MT, Caporaso N, Fernández-Tardón G, Zaridze D, Świątkowska B, Pándics T, Lissowska J, Fabianova E, Field JK, Mates D, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Casjens S, Pesch B, Brüning T, Behrens T

For the first time, two indices for general physical and psychosocial job demands were applied to lung cancer data. Higher job demands were associated with increasing lung cancer risks. The associations were stronger for physical job demands and weaker for psychosocial job demands. Psychosocial job demands did not contribute to explain the association between occupational social prestige and lung cancer.

**Affiliation:** Jan Hovanec, IPA, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. hovanec@ipa-dguv.de

**Key terms:** cancer; case-control; job index; lung cancer; occupational demand; psychosocial; smoking; social prestige; tumor subtype

This article in PubMed: www.ncbi.nlm.nih.gov/pubmed/33942106

**Additional material**

Please note that there is additional material available belonging to this article on the *Scandinavian Journal of Work, Environment & Health* -website.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
Scand J Work Environ Health. 2021;47(6):475-481. doi:10.5271/sjweh.3967

Application of two job indices for general occupational demands in a pooled analysis of
case-control studies on lung cancer

by Jan Hovanec, PhD,<fnref n="1" /> Jack Siemiatycki, PhD,<fnref n="2" /> David I Conway, PhD,<fnref n="3" /> Ann Olsson, PhD,<fnref n="4" /> Pascal Guenel, MD, PhD,<fnref n="5" /> Danièle Luce, PhD,<fnref n="6" /> Karl-Heinz Jöckel, PhD,<fnref n="7" /> Hermann Pohlabeln, PhD,<fnref n="8" /> Wolfgang Ahrens, PhD,<fnref n="8" />,<fnref n="9" /> Stefan Karrasch, MD,<fnref n="10" />,¹¹ Heinz-Erich Wichmann, PhD,¹²,¹³ Per Gustavsson, MD, PhD,¹⁴ Dario Consonni, MD, PhD,¹⁵ Franco Merletti, MD, PhD,¹⁶ Lorenzo Richiardi, MD, PhD,¹⁶ Lorenzo Simonato, MD,¹⁷ Cristina Fortes, PhD,¹⁸ Marie-Élise Parent, PhD,¹⁹ John R McLaughlin, PhD,²⁰ Paul Demers, PhD,²¹ Maria Teresa Landi, MD, PhD,²² Neil Caporaso, MD,²² Guillermo Fernández-Tardón, PhD,²³ David Zaridze, MD, PhD,²⁴ Beata Świątkowska, PhD,²⁵ Tamas Pándics, MD,²⁶ Jolanta Lissowska, PhD,²⁷ Eleonora Fabianova, MD, PhD,²⁸,²⁹ John K Field, PhD,³⁰ Dana Mates, MD,³¹ Vladimir Bencko, MD, PhD,³² Lenka Foretova, MD, PhD,³³ Vladimir Janout, PhD,³⁴ Hans Kromhout, PhD,³⁵ Roel Vermeulen, PhD,³⁵ Paolo Boffetta, MD, MPH,³⁶,³⁷ Kurt Straif, MD, PhD,<fnref n="4" /> Joachim Schüz, PhD,<fnref n="4" /> Swaantje Casjens, PhD,<fnref n="1" /> Beate Pesch, PhD,<fnref n="1" /> Thomas Brüning, MD, PhD,<fnref n="1" /> Thomas Behrens, MD, PhD<fnref n="1" />

Hovanec J, Siemiatycki J, Conway DI, Olsson A, Guenel P, Luce D, Jöckel K-H, Pohlabeln H, Ahrens W, Karrasch S, Wichmann H-E, Gustavsson P, Consonni D, Merletti F, Richiardi L, Simonato L, Fortes C, Parent M-E, McLaughlin JR, Demers P, Landi MT, Caporaso N, Fernández-Tardón G, Zaridze D, Świątkowska B, Pándics T, Lissowska J, Fabianova E, Field JK, Mates D, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Casjens S, Pesch B, Brüning T, Behrens T. Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer. *Scand J Work Environ Health*. 2021;47(6):475-481.

**Objectives** We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer.

**Methods** In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands – each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman’s Standard International Occupational Prestige Scale) were affected by adjustment for the job indices.

**Results** In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56–1.93), PSI 1.33 (95% CI 1.17–1.51)] and women [PHI 1.62 (95% CI 1.24–2.11), PSI 1.31 (95% CI 1.09–1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32–1.58) to 1.30 (95% CI 1.17–1.45)], but not PSI.

**Conclusions** Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.

**Key terms** job index; psychosocial; smoking; social prestige; tumor subtype.

<footnote n="1">¹ Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bochum, Germany.</footnote>

<footnote n="2">² University of Montreal, Hospital Research Center (CRCHUM) and School of Public Health, Montreal, Canada.</footnote>

<footnote n="3">³ Dental School, College of Medicine Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.</footnote>

<footnote n="4">⁴ International Agency for Research on Cancer (IARC/WHO), Lyon, France.</footnote>

<footnote n="5">⁵ Center for Research in Epidemiology and Population Health (CESP), Exposome and Heredity team, Inserm U1018, University Paris-Saclay, Villejuif, France.</footnote>

<footnote n="6">⁶ Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Pointe-à-Pitre, France.</footnote>

<footnote n="7">⁷ Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.</footnote>

<footnote n="8">⁸ Leibniz-Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.</footnote>

<footnote n="9">⁹ University Bremen, Faculty 3 - Mathematics and Computer Science, Bremen, Germany.</footnote>

<footnote n="10">¹⁰ Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.</footnote>
¹¹ Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.

¹² Institut für Medizinische Informatik Biometrie Epidemiologie, Ludwig Maximilians University, Munich, Germany.

¹³ Institut für Epidemiologie, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.

¹⁴ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

¹⁵ Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

¹⁶ Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy.

¹⁷ Laboratory of Public Health and Population Studies, Department of Molecular Medicine, University of Padova, Padova, Italy.

¹⁸ Epidemiology Unit, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy.

¹⁹ Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Université du Québec, Laval, Québec, Canada.

²⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

²¹ Cancer Care Ontario, Occupational Cancer Research Centre, Toronto, Canada.

²² Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

²³ Health Research Institute of the Principality of Asturias (ISPA), University of Oviedo and Ciber de Epidemiologia, CIBERESP, Oviedo, Spain.

²⁴ Department of Cancer Epidemiology and Prevention, N.N. Blokhin National Research Centre of Oncology, Moscow, Russia.

²⁵ Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.

²⁶ National Public Health Centre, Budapest, Hungary.

²⁷ M Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

²⁸ Regional Authority of Public Health, Preventive Occupational Medicine, Banska Bystrica, Slovakia.

²⁹ Catholic University, Faculty of Health, Ružomberok, Slovakia.

³⁰ Roy Castle Lung Cancer Research Programme, University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK.

³¹ National Institute of Public Health, Bucharest, Romania.

³² Charles University, 1st Faculty of Medicine, Institute of Hygiene and Epidemiology & General University Hospital, Prague, Czech Republic.

³³ Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Dept. of Cancer Epidemiology & Genetics, Brno, Czech Republic.

³⁴ Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.

³⁵ Environmental Epidemiology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.

³⁶ Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

³⁷ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Correspondence to: Jan Hovanec, IPA, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. [E-mail: hovanec@ipa-dguv.de]

Lung cancer risks are largely attributed to tobacco smoking, and occupational exposures to lung carcinogens (1, 2). Occupational social prestige and socioeconomic status are also identified as important risk factors, but – apart from supposed residual effects of smoking and exposure to occupational carcinogens – the pathways from occupational social determinants to lung cancer remain uncertain (3–6). Occupational conditions including psychosocial strain have been associated with elevated lung cancer risk (7) and may help to understand increased risks for occupations with a lower societal standing. Occupational prestige assigns a position in a perceived, hierarchical order of occupations that particularly captures work- and rank-related psychosocial demands. In addition, as an occupational indicator, it reflects material aspects of subject’s socioeconomic position (via income) and is directly linked with health outcomes by physical occupational hazards (8).

We extended analyses of the association between occupational prestige and lung cancer, previously identified in the international SYNERGY project (3), to investigate the role of further occupational exposures in this association. To cover a broad range of exposures and with regard to available job histories in SYNERGY, we applied two job-title based indices for general occupational demands (9) that have not yet been applied in the context of lung cancer. One was an index for environmental/physical demands, potentially also indicating

effects of occupational carcinogens, and the other an index for psychosocial occupational demands. To our knowledge, to date, psychosocial demands have not been analyzed together with occupational prestige and lung cancer.

Before extending analysis of occupational prestige, we examined if the two occupational indices themselves were associated with lung cancer and thus appropriate for further analysis. This could additionally show if the job-title based indices are suitable for facilitated assessment of work environment risks when detailed occupational exposure information is not available.

Thus, in the first step, we analyzed the association of the two indices for general job demands and lung cancer and, in the second step, the role of these demands in the association of occupational prestige and lung cancer.

## Methods

The detailed methodology employed in SYNERGY has been published elsewhere (10). For this analysis of lung cancer and job indices, we included 13 European and Canadian case-control studies with 19 study centres of the SYNERGY dataset. Details and distribution of cases and controls are included in the supplementary material (www.sjweh.fi/article/3967), table S1. After exclusion
of subjects with largely (>50%) missing or invalid occupa-
tional histories (N=1236) and missing smoking infor-
mation (N=25), the dataset included 37 726 men and
women (16 909 cases, 20 817 controls). To extend the
previous social prestige analysis (3), we adapted inclu-
sion criteria so that prestige analyses were restricted to
12 studies (18 study centres) and male gender (11 420
cases, 14 130 controls).

Job demands were assigned by two indices for gen-
eral job demands (9). These indices were constructed
and validated using German survey data for men and
women and contain two/three dimensions of occupa-
tional demands: (i) a physical index (PHI) for ergonomic
demands and environmental exposures (including acid,
dust, fumes, climatic conditions, radiation, environmen-
tal tobacco smoke (ETS), dirt, noise, vibrations, low/
glaring light, or need for protective clothing) and (ii) a
psychosocial index (PSI) for mental (eg, overload, dis-
ruptions, low error tolerance), social (eg, lacking work
control, conflicts, lacking support), and temporal (eg,
on-call service, excessive working hours, shift work)
demands. Originally, both indices may be summarized
to an overall index, which we did not apply due to its
high correlation with the PHI (Spearman correlation
coefficient 0.95). We assigned both indices (range of
1–10 from low to high demands) to the subjects’ entire
occupational histories and calculated time-weighted
average (TWA) scores. TWA-scores were categorized
into four categories: low (1, 2), lower middle (3–5),
upper middle (6–8), and high (9, 10) demands (9). In
sensitivity analyses, we recalculated scores disregarding
the last ten years before diagnosis/interview to consider
cancer latency. In the opposite direction, we used the
last job to rather consider job demand effects on tumor
promotion or progression.

To estimate lung cancer risks for job-demand indices
(PHI, PSI), we calculated odds ratios (OR) with 95%
confidence intervals (CI) by unconditional multiple
logistic regression in a pooled analysis of all studies.
We first adjusted for age (ln(age)) and study centre, then
added smoking habits (smoking status [never (<1 pack-
year in lifetime), former, current (including quitting
smoking before <2 years), and other type of tobacco,
including subdivision of former smokers by time since
quitting smoking (2–7, 8–15, 16–25, >25 years)] and
cigarette pack-years [ln pack-years + 1)], and finally
added ever employment in occupations and industries
known to be associated with lung cancer with potential
exposure to carcinogens (‘list A’ occupations) (12, 13)
(final model). OR were estimated separately for main
histological lung cancer subtypes [squamous cell carci-
noma (SQCC), small cell lung cancer (SCLC), adeno-
carcinoma (ADC)]. In addition, job-demand indices
were included as continuous variables to test for linear
trends. To consider effects of individual studies, we

compared results from the pooled analyses with meta-
analyses (random-effects model) using the Paule–Mandel heterogeneity variance estimator (14) and displayed heterogeneity by I².

For the prestige analysis, we adopted TWA prestige
scores of Treiman’s Standard International Occupational
Prestige Scale (SIOPS) (15), based on subject’s occupa-
tional history, and categorized it into low, medium, and
high TWA prestige (3). We repeated models according to
the original publication, adjusting for factors mentioned
above (final model), education (<6, 6–9, 10–13, >13
years), and additionally the respective job index.

All calculations were performed with SAS, version
9.4 (SAS Institute Inc, Cary, NC, USA).

Results

Descriptive information on the study population is
shown in table 1. Both indices revealed higher job
demands for cases than controls, with less pronounced
differences for women and psychosocial exposures.
TWA prestige was lower among cases.

In regression analysis (table 2), we found a gradient
of lung cancer risks for increasing PHI in men [high
versus low OR 1.74 (95% CI 1.56–1.93) and women
(OR 1.62 (95% CI 1.24–2.11)] in the final models. Esti-
mates for highest versus lowest PSI were lower than for
PHI in men [OR 1.33 (95% CI 1.17–1.51)] and women
[OR 1.31 (95% CI 1.09–1.56)]. Despite consistently
significant tests for trend, risks were elevated just for
the highest psychosocial demands among women. Only
among men, risks decreased particularly after adjust-
ment for smoking, and less after adjustment for ‘list A’
industries/occupations. Increased risks for higher job
demands were detected for SQCC and SCLC, but not
for ADC. Estimates of the random-effects model were
slightly reduced compared to those of the one-stage
regression [high versus low PHI: men OR 1.61 (95%
CI 1.30–1.99), women OR 1.53 (95% CI 1.14–2.06)
PSI: men OR 1.29 (95% CI 1.11–1.50), women OR 1.23
(95% CI 0.89–1.69)]. Statistically significant heteroge-
neity between the studies was only found for PHI in men
(I²=60%, P<0.001). Both sensitivity analyses, assuming
10-year lag time and restriction to the last job, showed
slightly reduced estimates for men and women, except
slightly elevated OR for PHI for the last job among
women (supplementary table S2).

In the analysis of occupational prestige in men, lung
cancer risks for low and medium versus high prestige
[OR 1.44 (95% CI 1.32–1.58) and 1.23 (95% CI 1.13–
1.34), respectively) were reduced by additional adjust-
ment for PHI (low prestige 1.30 (95% CI 1.17–1.45),
medium prestige 1.14 (95% CI 1.04–1.26)], but not for
<table><caption>Table 1. Study population. [IQR=interquartile range].</caption><thead><tr><th rowspan="3"></th><th colspan="4">Men</th><th colspan="4">Women</th></tr><tr><th colspan="2">Cases (N=13 791)</th><th colspan="2">Controls (N=16 564)</th><th colspan="2">Cases (N=3118)</th><th colspan="2">Controls (N=4253)</th></tr><tr><th>N (%)</th><th>Median (IQR)</th><th>N (%)</th><th>Median (IQR)</th><th>N (%)</th><th>Median (IQR)</th><th>N (%)</th><th>Median (IQR)</th></tr></thead><tbody><tr><td>Age (years)</td><td></td><td>63 (56-69)</td><td></td><td>63 (56-69)</td><td></td><td>61 (53-69)</td><td></td><td>61 (52-69)</td></tr><tr><td>Smoking status</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Non-smoker</td><td>393 (2.9)</td><td></td><td>4489 (27.1)</td><td></td><td>877 (28.1)</td><td></td><td>2689 (63.2)</td><td></td></tr><tr><td>Former smoker</td><td>4829 (35.0)</td><td></td><td>7052 (42.6)</td><td></td><td>591 (19.0)</td><td></td><td>737 (17.3)</td><td></td></tr><tr><td>Current smoker</td><td>8423 (61.1)</td><td></td><td>4680 (28.3)</td><td></td><td>1650 (52.9)</td><td></td><td>826 (19.4)</td><td></td></tr><tr><td>Other types of tobacco only</td><td>146 (1.1)</td><td></td><td>343 (2.1)</td><td></td><td>0 (0)</td><td></td><td>1 (0)</td><td></td></tr><tr><td>Cigarette pack-years in former and current smokers</td><td></td><td>39 (27-54)</td><td></td><td>25 (12-40)</td><td></td><td>31 (20-45)</td><td></td><td>17 (8-30)</td></tr><tr><td>Subtype of lung cancer</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Squamous cell carcinoma</td><td>5904 (42.8)</td><td></td><td></td><td></td><td>627 (20.1)</td><td></td><td></td><td></td></tr><tr><td>Small cell</td><td>2226 (16.1)</td><td></td><td></td><td></td><td>502 (16.1)</td><td></td><td></td><td></td></tr><tr><td>Adenocarcinoma</td><td>3391 (24.6)</td><td></td><td></td><td></td><td>1354 (43.4)</td><td></td><td></td><td></td></tr><tr><td>Other/mixed</td><td>1401 (15.9)</td><td></td><td></td><td></td><td>622 (20.0)</td><td></td><td></td><td></td></tr><tr><td>Missing</td><td>80 (0.6)</td><td></td><td></td><td></td><td>13 (0.4)</td><td></td><td></td><td></td></tr><tr><td>Ever worked in 'list A' occupations/industries<sup>a</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Yes</td><td>2038 (14.8)</td><td></td><td>1559 (9.4)</td><td></td><td>80 (2.6)</td><td></td><td>53 (1.3)</td><td></td></tr><tr><td>No</td><td>11753 (85.2)</td><td></td><td>15005 (90.6)</td><td></td><td>3038 (97.4)</td><td></td><td>4200 (98.8)</td><td></td></tr><tr><td>Physical job exposure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Low</td><td>854 (6.2)</td><td></td><td>1743 (10.5)</td><td></td><td>212 (6.8)</td><td></td><td>332 (7.8)</td><td></td></tr><tr><td>Lower middle</td><td>2727 (19.8)</td><td></td><td>4906 (29.6)</td><td></td><td>1214 (38.9)</td><td></td><td>1963 (46.2)</td><td></td></tr><tr><td>Upper middle</td><td>4739 (34.4)</td><td></td><td>5187 (31.3)</td><td></td><td>1358 (43.6)</td><td></td><td>1611 (37.9)</td><td></td></tr><tr><td>High</td><td>5471 (39.7)</td><td></td><td>4728 (28.5)</td><td></td><td>334 (10.7)</td><td></td><td>347 (8.2)</td><td></td></tr><tr><td>Psychosocial job exposure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Low</td><td>740 (5.4)</td><td></td><td>1398 (8.4)</td><td></td><td>483 (15.5)</td><td></td><td>695 (16.3)</td><td></td></tr><tr><td>Lower middle</td><td>4356 (31.6)</td><td></td><td>5695 (34.4)</td><td></td><td>691 (22.2)</td><td></td><td>1020 (24.0)</td><td></td></tr><tr><td>Upper middle</td><td>6934 (50.3)</td><td></td><td>7528 (45.5)</td><td></td><td>1220 (39.1)</td><td></td><td>1797 (42.3)</td><td></td></tr><tr><td>High</td><td>1761 (12.8)</td><td></td><td>1943 (11.7)</td><td></td><td>724 (23.2)</td><td></td><td>741 (17.4)</td><td></td></tr><tr><td>Occupational prestige<sup>b</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>High</td><td>2209 (19.3)</td><td></td><td>4586 (32.5)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Medium</td><td>3975 (34.8)</td><td></td><td>4847 (34.3)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Low</td><td>5236 (45.9)</td><td></td><td>4697 (33.2)</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

PSI [low prestige 1.46 (95% CI 1.33–1.61), medium prestige 1.24 (95% CI 1.14–1.35)].

Discussion

In our analysis of lung cancer and job-demand indices in men and women, we found elevated lung cancer risks in particular for high physical job demands and less strong associations for psychosocial job demands. Adjustment for PHI reduced lung cancer risks of men with low occupational prestige but adjustment for PSI did not influence results.

We made use of the large SYNERGY database with its detailed smoking information and occupational histories. Previous SYNERGY analyses have identified possible residual effects of smoking due to potential information bias, lacking data on ETS, and possibly the inclusion of occasional smokers among non-smokers (defined by <1 cigarette pack-year) (3, 4). Similarly, we confirmed higher risks for higher job demands in the subtypes of lung cancer that are particularly related to smoking (SQCC, SCLC) and decreased risks for ADC (3, 4, 16). A potential limitation lies in the German

database of the job indices, which we applied to international data. However, these data were all from (post-) industrial countries (Europe and Canada), and results of the random-effects model, considering study-specific variances, were similar to pooled estimates.

The applied job indices were constructed to allow assignment of general occupational demands on the basis of occupational job codes in the absence of more detailed information (9), which are included in SYNERGY for selected occupational carcinogens. We considered occupational lung carcinogens in general by ever exposure in 'list A' industries and occupations, a simplified exposure assessment. Occupational carcinogens therefore may also mainly account for the elevated risks for higher physical job index, ie, manual jobs, which may also include exposure to occupational fumes, dusts, and ETS. The reduction of risks of lower prestige occupations by adjustment for PHI might account for these previously uncaptured exposures to occupational carcinogens. Therefore, the physical index appears as crude but easily applicable proxy for occupational lung cancer hazards when only job titles were solicited.

Associations with lung cancer were lower for psychosocial compared to physical job demands. However, the PSI includes indicators for potential (lung) cancer

<footnote>a Occupations and industries known to be associated with lung cancer.</footnote>

<footnote>b Analysis restricted to men and with reduced data set (11 420 cases and 14 130 controls).</footnote>
<table><caption>**Table 2.** Associations between lung cancer and job-exposure indices. [ADC=adeno carcinoma; PHI=physical index; PSI=psychosocial index; SCLC=small cell lung cancer; SQCC=squamous cell carcinoma]</caption><thead><tr><th rowspan="2">Job index</th><th colspan="3">Men</th><th colspan="3">Women</th></tr><tr><th>Cases</th><th>Controls</th><th>OR (95% CI)<sup>a</sup></th><th>OR (95% CI)<sup>b</sup></th><th>Cases</th><th>Controls</th><th>OR (95% CI)<sup>a</sup></th><th>OR (95% CI)<sup>b</sup></th><th>OR (95% CI)<sup>c</sup></th></tr></thead><tbody><tr><td colspan="10"><strong>All lung cancers</strong></td></tr><tr><td colspan="10"><strong>PHI</strong></td></tr><tr><td>Low</td><td>854</td><td>1743</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>212</td><td>332</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>2727</td><td>4906</td><td>1.08 (0.98-1.19)</td><td>1.06 (0.95-1.18)</td><td>1214</td><td>1963</td><td>0.99 (0.81-1.19)</td><td>1.07 (0.86-1.33)</td><td>1.07 (0.86-1.33)</td></tr><tr><td>Upper middle</td><td>4739</td><td>5187</td><td>1.82 (1.66-1.99)</td><td>1.47 (1.32-1.63)</td><td>1358</td><td>1611</td><td>1.30 (1.08-1.58)</td><td>1.34 (1.08-1.66)</td><td>1.32 (1.06-1.64)</td></tr><tr><td>High</td><td>5471</td><td>4728</td><td>2.27 (2.07-2.49)</td><td>1.82 (1.64-2.02)</td><td>334</td><td>347</td><td>1.44 (1.14-1.82)</td><td>1.66 (1.27-2.16)</td><td>1.62 (1.24-2.11)</td></tr><tr><td colspan="10"><strong>PSI</strong></td></tr><tr><td>Low</td><td>740</td><td>1398</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>483</td><td>695</td><td>1.00<sup>d</sup></td><td>1.00<sup>e</sup></td><td>1.00<sup>w</sup></td></tr><tr><td>Lower middle</td><td>4356</td><td>5695</td><td>1.47 (1.33-1.62)</td><td>1.29 (1.15-1.44)</td><td>691</td><td>1020</td><td>0.98 (0.84-1.15)</td><td>1.01 (0.85-1.20)</td><td>1.00 (0.84-1.19)</td></tr><tr><td>Upper middle</td><td>6934</td><td>7528</td><td>1.75 (1.59-1.93)</td><td>1.41 (1.26-1.57)</td><td>1220</td><td>1797</td><td>0.98 (0.86-1.13)</td><td>0.97 (0.83-1.14)</td><td>0.96 (0.82-1.12)</td></tr><tr><td>High</td><td>1761</td><td>1943</td><td>1.75 (1.56-1.95)</td><td>1.37 (1.21-1.56)</td><td>724</td><td>741</td><td>1.46 (1.24-1.71)</td><td>1.32 (1.10-1.58)</td><td>1.31 (1.09-1.56)</td></tr><tr><td colspan="10"><strong>SQCC</strong></td></tr><tr><td colspan="10"><strong>PHI</strong></td></tr><tr><td>Low</td><td>283</td><td>1743</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>26</td><td>332</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>1061</td><td>4906</td><td>1.21 (1.05-1.40)</td><td>1.18 (1.01-1.38)</td><td>227</td><td>1963</td><td>1.43 (0.93-2.20)</td><td>1.50 (0.93-2.40)</td><td>1.50 (0.93-2.40)</td></tr><tr><td>Upper middle</td><td>2063</td><td>5187</td><td>2.27 (1.98-2.61)</td><td>1.84 (1.58-2.13)</td><td>306</td><td>1611</td><td>2.08 (1.36-3.20)</td><td>2.26 (1.41-3.62)</td><td>2.26 (1.41-3.62)</td></tr><tr><td>High</td><td>2497</td><td>4728</td><td>2.99 (2.60-3.42)</td><td>2.38 (2.05-2.76)</td><td>68</td><td>347</td><td>1.93 (1.18-3.16)</td><td>2.47 (1.44-4.25)</td><td>2.47 (1.43-4.25)</td></tr><tr><td colspan="10"><strong>PSI</strong></td></tr><tr><td>Low</td><td>295</td><td>1398</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>81</td><td>695</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>1813</td><td>5695</td><td>1.54 (1.34-1.77)</td><td>1.34 (1.15-1.56)</td><td>117</td><td>1020</td><td>0.91 (0.67-1.24)</td><td>1.03 (0.73-1.46)</td><td>1.03 (0.73-1.45)</td></tr><tr><td>Upper middle</td><td>3043</td><td>7528</td><td>1.89 (1.65-2.16)</td><td>1.50 (1.30-1.74)</td><td>272</td><td>1797</td><td>1.21 (0.92-1.58)</td><td>1.35 (0.99-1.83)</td><td>1.34 (0.99-1.82)</td></tr><tr><td>High</td><td>753</td><td>1943</td><td>1.85 (1.59-2.16)</td><td>1.41 (1.19-1.68)</td><td>157</td><td>741</td><td>1.64 (1.22-2.21)</td><td>1.59 (1.14-2.23)</td><td>1.59 (1.14-2.22)</td></tr><tr><td colspan="10"><strong>SCLC</strong></td></tr><tr><td colspan="10"><strong>PHI</strong></td></tr><tr><td>Low</td><td>131</td><td>1743</td><td>1.00<sup>d</sup></td><td>1.00<sup>e</sup></td><td>39</td><td>332</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>406</td><td>4906</td><td>1.05 (0.85-1.29)</td><td>1.01 (0.81-1.26)</td><td>161</td><td>1963</td><td>0.76 (0.52-1.11)</td><td>0.77 (0.49-1.19)</td><td>0.76 (0.49-1.18)</td></tr><tr><td>Upper middle</td><td>791</td><td>5187</td><td>1.99 (1.64-2.42)</td><td>1.52 (1.23-1.87)</td><td>238</td><td>1611</td><td>1.29 (0.89-1.88)</td><td>1.31 (0.85-2.01)</td><td>1.29 (0.84-1.98)</td></tr><tr><td>High</td><td>898</td><td>4728</td><td>2.47 (2.04-3.00)</td><td>1.90 (1.55-2.34)</td><td>64</td><td>347</td><td>1.70 (1.09-2.65)</td><td>2.05 (1.21-3.48)</td><td>1.97 (1.16-3.34)</td></tr><tr><td colspan="10"><strong>PSI</strong></td></tr><tr><td>Low</td><td>95</td><td>1398</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>65</td><td>695</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>720</td><td>5695</td><td>1.81 (1.45-2.26)</td><td>1.56 (1.23-1.98)</td><td>109</td><td>1020</td><td>1.15 (0.83-1.60)</td><td>1.19 (0.82-1.74)</td><td>1.18 (0.81-1.72)</td></tr><tr><td>Upper middle</td><td>1126</td><td>7528</td><td>2.17 (1.74-2.70)</td><td>1.66 (1.31-2.09)</td><td>197</td><td>1797</td><td>1.18 (0.87-1.59)</td><td>1.27 (0.90-1.80)</td><td>1.24 (0.88-1.76)</td></tr><tr><td>High</td><td>285</td><td>1943</td><td>2.21 (1.73-2.82)</td><td>1.65 (1.27-2.15)</td><td>131</td><td>741</td><td>2.10 (1.52-2.90)</td><td>1.98 (1.36-2.88)</td><td>1.93 (1.32-2.82)</td></tr><tr><td colspan="10"><strong>ADC</strong></td></tr><tr><td colspan="10"><strong>PHI</strong></td></tr><tr><td>Low</td><td>259</td><td>1743</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>86</td><td>332</td><td>1.00<sup>e</sup></td><td>1.00<sup>e</sup></td><td>1.00<sup>e</sup></td></tr><tr><td>Lower middle</td><td>841</td><td>4906</td><td>1.11 (0.96-1.30)</td><td>1.11 (0.95-1.31)</td><td>575</td><td>1963</td><td>1.06 (0.81-1.37)</td><td>1.10 (0.84-1.45)</td><td>1.10 (0.83-1.45)</td></tr><tr><td>Upper middle</td><td>1095</td><td>5187</td><td>1.41 (1.22-1.64)</td><td>1.17 (1.00-1.38)</td><td>551</td><td>1611</td><td>1.24 (0.95-1.61)</td><td>1.25 (0.95-1.65)</td><td>1.24 (0.94-1.64)</td></tr><tr><td>High</td><td>1196</td><td>4728</td><td>1.65 (1.42-1.91)</td><td>1.37 (1.17-1.60)</td><td>142</td><td>347</td><td>1.45 (1.05-1.99)</td><td>1.60 (1.15-2.24)</td><td>1.57 (1.12-2.20)</td></tr><tr><td colspan="10"><strong>PSI</strong></td></tr><tr><td>Low</td><td>232</td><td>1398</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>239</td><td>695</td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td><td>1.00<sup>d</sup></td></tr><tr><td>Lower middle</td><td>1105</td><td>5695</td><td>1.21 (1.03-1.41)</td><td>1.07 (0.91-1.27)</td><td>306</td><td>1020</td><td>0.92 (0.75-1.12)</td><td>0.92 (0.74-1.13)</td><td>0.91 (0.74-1.12)</td></tr><tr><td>Upper middle</td><td>1625</td><td>7528</td><td>1.34 (1.15-1.57)</td><td>1.11 (0.94-1.30)</td><td>523</td><td>1797</td><td>0.87 (0.73-1.04)</td><td>0.87 (0.72-1.05)</td><td>0.86 (0.71-1.04)</td></tr><tr><td>High</td><td>429</td><td>1943</td><td>1.35 (1.13-1.61)</td><td>1.10 (0.91-1.32)</td><td>286</td><td>741</td><td>1.17 (0.95-1.44)</td><td>1.09 (0.87-1.35)</td><td>1.08 (0.87-1.34)</td></tr></tbody></table>

risk factors, in particular chronic stress. Our results were similar to one study on lung cancer and work-related stress among men (7), while other studies did not find significantly increased risks (17, 18). We found an overall pattern of higher lung cancer risks for men, increasing with job demands, but no increase of risks for women with moderate psychosocial demands. The reasons for this finding remain unclear also because the job indices were constructed for men and women.

Generally, methodological issues in the assignment

of job demands are critical in occupational cancer risk estimation as shown for two analyses of oesophageal cancer and psychosocial exposures (19, 20): one of which used personal questionnaires on job strain exposure and did not find an association for higher job strain (19), whereas in contrast, increased risks were detected when deducing job strain from job titles (20). However, in comparison to physical demands, derivation of psychosocial dimensions by objective job titles may be limited and dependent more on individual characteristics

<footnote>a Adjusted for ln(age) and study centre.</footnote>

<footnote>b Adjusted for ln(age), study centre, smoking status including time since quitting (non-smoker, quitted 2-7, 8-15, 16-25, >26 years before interview/diagnosis, current smoker, other types of tobacco only) and cigarette pack-years (ln(pack-years+1)).</footnote>

<footnote>c Adjusted for ln(age), study centre, smoking status including time since quitting (non-smoker, quitted 2-7, 8-15, 16-25, >26 years before interview/diagnosis, current smoker, other types of tobacco only) and cigarette pack-years (ln(pack-years+1)) and ever employment in occupations and industries with potential exposure to carcinogens.</footnote>

<footnote>d P for linear trend <0.001.</footnote>

<footnote>e P for linear trend <0.05.</footnote>
(9). This could explain why the observed associations were lower compared to the physical demands. This limitation has to be considered particularly for our analysis of occupational prestige and lung cancer, ie, we could have missed possible effects by adjusting for psychosocial job demands due to insufficient capture of these demands by job titles.

## Concluding remarks

The job-title-based indices suggested a role of occupational demands for lung cancer, beyond exposure to known occupational carcinogens, and their application in understanding work environment risks in the absence of detailed quantitative occupational exposure information. Lung cancer risks were particularly increased for higher physical job demands, likely due to capturing undetermined effects of occupational lung carcinogens. The index for psychosocial demands was less clearly associated with lung cancer, and – in contrast to physical demands – did not contribute to clarify the association of occupational prestige and lung cancer.

## Acknowledgements

Isabelle Stücker will be remembered for her professionalism and generosity regarding the SYNERGY project.

## Competing interests

The authors do not declare any conflict of interest.

JH, SC, BP, TBr, and TB as staff of the Institute for Prevention and Occupational Medicine (IPA), are employed at the "Berufsgenossenschaft Rohstoffe und chemische Industrie" (BG RCI), a public body, which is a member of the study's main sponsor, the German Social Accident Insurance. IPA is an independent research institute of the Ruhr University Bochum. The authors are independent from the German Social Accident Insurance in study design, access to the collected data, responsibility for data analysis and interpretation, and the right to publish. The views expressed in this paper are those of the authors and not necessarily those of the sponsor.

Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

## Funding

The German Social Accident Insurance supported this study (grant number FP 271).

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Received for publication; 11 February 2021