Occupational risk variation of nasopharyngeal cancer in the Nordic countries

doi:10.21203/rs.3.rs-1636886/v1

Download PDF

Research Article

Occupational risk variation of nasopharyngeal cancer in the Nordic countries

https://doi.org/10.21203/rs.3.rs-1636886/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: The aim of this study was to estimate occupational risk variation in the incidence of nasopharyngeal cancer (NPC) in a large population-based cohort of the Nordic Occupational Cancer (NOCCA) study.

Methods: This study is based on a cohort of almost 15 million persons from Denmark, Finland, Iceland, Norway and Sweden, with 2898 nasopharyngeal cancer cases diagnosed in 1961-2005. The data on occupations were gathered from population censuses and cancer data from the national cancer registries. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were estimated using the national NPC incidence rates as the reference.

Results: There were 1980 male and 918 female NPC patients. The highest SIRs of NPC were observed among male waiters (SIR 3.69, 95% CI 1.91–6.45) and cooks and stewards (SIR 2.24, 95% CI 1.16–3.91). Among women, launderers had the highest SIR of NPC (2.04, 95% CI 1.02–3.65). Significantly decreased SIRs were found among male farmers (SIR 0.79, 95% CI 0.68–0.92) and male textile workers (SIR 0.49, 95% CI 0.22–0.93).

Conclusions: This study suggests that NPC may be associated with several work-related exposure agents such as smoking, kitchen air pollution and solvents. In future, occupational exposure-risk relations should be studied to understand more about causality and to assess effective prevention strategies.

incidence

cohort

nasopharyngeal cancer

occupation

risk factor

Worldwide, close to 850 000 new head and neck squamous cell carcinoma (HNSCC) cases are diagnosed annually and approximately 130 000 of these are nasopharyngeal carcinomas (NPC) (1). The NPC incidence is much higher in South-Asia than in Europe and North America (1, 2). Majority of NPC cases in endemic areas are non-keratinizing and predominantly associated with Epstein-Barr virus (EBV) (3). Another major risk factors for NPC is tobacco smoking (4–6).

Exposure to occupation-related agents such as formaldehyde and chlorophenol, wood and cotton dust, smokes, and combustion have been associated with the development of NPC (7–12). Upper airways including nasopharynx are directly exposed to these often work-related exposures. For example, occupational exposure to formaldehyde has been classified by the International Agency of Cancer as a causing NPC (13). Wood dust exposure is likewise a risk factor of NPC, especially when the exposure is long-timed (14–19). Cotton dust, which is common in textile industry, is another exposure that has been linked with NPC, but evidence remains inconclusive (20, 21).

The aim of this study was to identify occupations linked to NPC in the five Nordic countries.

This study is based on NPC patients included in the Nordic Occupational Cancer (NOCCA) study cohort. The NOCCA cohort includes census participants covering a total of 14.9 million persons from Denmark, Finland, Iceland, Norway and Sweden followed up between 1961 and 2005 (22).

Subjects aged 30–64 years old and alive on January 1 of the year after the first available census were linked to their occupational data and cancer data with help of the unique personal identity codes given to all residents of the Nordic countries (23). The follow-up time of each individual started from the year following the first available census record of the person and ended at the date of emigration, death or at the end of the following years: Finland and Sweden 2005, Iceland 2004 and Norway and Denmark 2003 (24). For the present study used the occupational data were origilally coded according to Nordic Occupational Classification (NYK), International Standard of Classification of Occupations (ISCO) versions 58 and 68, or a special Danish classification were classified into 54 occupational categories. A detailed description of the NOCCA cohort and occupational data are presented in previous reports (23, 25).

Data on NPCs (International Classification of Diseases, 7th Revision, code 146) were obtained from the cancer registry of each country. During the follow-up period, all cancer registries received clinical notifications from hospitals and all except Denmark also from cancer laboratories in the public and private sectors (26).

Standardized incidence ratio (SIR) was used as the measure of relative risk of NPC. SIR is the ratio of the observed and expected numbers of cases. The expected number of cases in each country, gender, 5-year calendar period and 5-year age category was calculated by multiplying the number of person-years in the stratum by the respective national incidence rate of NPC. Exact 95% confidence intervals (CI) were determined by Poisson distribution and SIR was considered as statistically significant if its CI did not include 1.0. The study has permissions as required in each of the Nordic countries.

Altogether, 2898 patients diagnosed with NPC were observed during the follow-up of the present study. There were 1980 male and 918 female NPC patients. The majority (n = 1524) of the patients were from Sweden and only 18 patients were from Iceland.

The highest SIR of NPC was found among male waiters in the whole Nordic cohort (SIR 3.69, 95% CI 1.91–6.45) and separately in Norway (SIR 4.79, 95% CI 1.30–12.25) and Denmark (SIR 6.81, 95% CI 2.21–15.88) (Table 1). The SIR for female waiters was not significantly elevated (Table 2).

The SIR was significantly elevated among male cooks and stewards in the entire Nordic cohort (SIR 2.24, 95% CI 1.16–3.91) and in the Swedish cohort (SIR 2.68, 95% CI 1.08–5.53). NPC incidence was elevated among male bricklayers in the entire Nordic cohort (SIR 1.80, 95% CI 1.20–2.60) and separately in the Danish cohort (SIR 2.53, 95% CI 1.26–4.52). Finnish male administrators and sales agents had significantly elevated SIRs but similar findings were not observed in other Nordic countries.

Among females, launderers had the highest and significantly elevated SIR in the entire cohort (SIR 2.04, 95% CI 1.02–3.65) and separately in the Norwegian cohort (SIR 5.38, 95% CI 1.47–13.79

Significantly decreased incidence of NPC was found among Nordic male farmers (SIR 0.79, 95% CI 0.68–0.92) and male textile workers (SIR 0.49, 95% CI 0.22–0.93). The SIR for farmers was especially low in Finland and Denmark (SIR 0.58, 95% CI 0.36–0.88 and 0.65, 95% CI 0.42–0.95, respectively).

Male fishermen in Norway had a significantly elevated SIR (1.64, 95% CI 1.03–2.49, Table 1). Male fishermen in Denmark and Finland also had elevated SIRs but these findings were not statistically significant.

This study provides new evidence on occupational risk variation of NPC in the Nordic countries. Norwegian, Finnish and Swedish fishermen had elevated SIRs of NPC in the present study which to our knowledge is a new finding. Salted fish is a confirmed risk factor for NPC and commonly used in Southern Asia (27), but we no evidence whether fishermen in the three Nordic countries consume more salted fish than the reference population. Fishermen might have been exposed to off-gas from fermented fish, especially in the old time where the storage tanks on fishing boards were emptied manually.

Cooks and stewards showed elevated SIRs in the present study. Previously the elevated risk for lung cancer among cooks has been related to indoor air pollution which may also be one link between cooks and NPC (28). In addition, wood combustion has been found to be a potential risk factor for NPC and a potential exposure agent for cooks (29).

In some previous studies frequent exposure to cotton dust has been associated with elevated risk of NPC (12, 21, 30). We did not find an elevated SIR among female textile workers, and there was a statistically significant decreased SIR for male textile workers. Thus, this study does not support a such evidence.

We found that female launderers had statistically significantly higher risk of NPC than the population on average. In drycleaning, tetrachloroethylene is the dominant solvent used in the world and in the Nordic countries (31).

The International Agency for Research on Cancer (IARC) classified formaldehyde and wood dust as occupational carcinogens in relation to NPC (32). In the present study, exposure to these agents is most likely among wood workersbut we did not find elevated SIRs among them (33). NPC incidence was significantly elevated among male waiters. Previously Nordic waiters have been related to elevated incidence of lung cancer, oral cancer and pharyngeal cancer (34). An increased risk of death from NPC was reported among waiters in China (35). One explanation may be that waiters have been exposed to passive and active tobacco smoke, which has also been associated with NPC (4, 36). Prior to smoking restrictions in bars and restaurants, waiters worked in a smoke-filled environment and had higher proportion of active smokers than other workers (34). Several studies have shown a modestly increased risk of NPC associated with tobacco smoking, and a meta-analysis indicated an approximately 60% increased risk for NPC among smokers (37, 38). In Finland and Norway, smoke-free legislation in restaurants has shown effective results in the decrease of passive smoking exposure (36, 39) and improving lung function [40] among waiters. Therefore it is expected that the excess incidence of NPC among restaurant staff will get smaller in the future.

Strengths of this study include large cohorts with nationwide population-based data, long follow-up period and high quality registry data (26). A limitation of the present study was the missing stratification of NPCs by histological subtype, and the lack of information on factors not directly related to occupation.

The present study suggests that certain work-related exposures such as passive smoking, kitchen air pollution and solvents may be associated with NPC. In future, exposure-risk relations should be studied to understand more about causality and to assess effective prevention strategies against NPC.

EBV: Epstein-Barr virus

CI: Confidence interval

HNSCC: Head and neck squamous cell carcinoma

HPV: Human papillomavirus

ISCO: International Standard of Classification of Occupations

NOCCA: Nordic Occupational Cancer Study

NPC: Nasopharyngeal carcinoma

NYK: Nordic Occupational Classification

SIR: Standardized incidence ratio

Ethics approval and consent to participate

The current study was based on data from existing registries and did not include any human intervention. The NOCCA study had ethics approvals and permissions as required in each of the participating countries at the time of data collection. The data were anonymized before using them in the analyses. Study participants were not contacted during the execution of the study.

Consent for publication

Not applicable.

Availability of data and materials

The tabulated datasets generated and/or analysed during the current study are available in the NOCCA repository, https://astra.cancer.fi/NOCCA/.

Competing interests

The authors declare no competing interests.

Funding

The data collection for the NOCCA study was supported by the Nordic Cancer Union.

Authors´ contributions

Timo Carpén, Evelina Gille, Lalle Hammastedt-Nordenvall and Antti Mäkitie; interpretation of results and writing of the manuscript; Elsebeth Lynge and Johnni Hansen: responsible for the data accuracy and SIR estimates of Denmark; Sanna Heikkinen current principal investigator in NOCCA study in Finland and leader of the NOCCA network; Jenny Selander: current principal investigator in NOCCA study in Sweden; Ingrid Sivesind Mehlum: current principal investigator in NOCCA study in Norway; Jóhanna Eyrún Torfadottir: current principal investigator in NOCCA study in Iceland; Eero Pukkala: design of the study, data analysis, interpretation of results, and writing the manuscript. All authors have commented the manuscript and read and approved the final version.

Acknowledgements

We thank the Nordic Cancer Union for the financial support and Jan Ivar Martinsen (Cancer Registry of Norway) for data management and statistical analyses of the data.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. 2018;68(6):394–424.
Tang LL, Chen WQ, Xue WQ, He YQ, Zheng RS, Zeng YX, et al. Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett. 2016;374(1):22–30.
Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer. 2014;33(12):581–90.
Chang ET, Liu Z, Hildesheim A, Liu Q, Cai Y, Zhang Z, et al. Active and passive smoking and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China. Am J Epidemiol. 2017;185(12):1272–80.
West S, Hildesheim A, Dosemeci M. Non-viral risk factors for nasopharyngeal carcinoma in the Philippines: results from a case-control study. Int J Cancer. 1993;55(5):722–7.
Fernandes Q, Merhi M, Raza A, Inchakalody VP, Abdelouahab N, Zar Gul AR, et al. Role of Epstein-Barr virus in the pathogenesis of head and neck cancers and its potential as an immunotherapeutic target. Front Oncol. 2018;8:257.
Beane Freeman LE, Blair A, Lubin JH, Stewart PA, Hayes RB, Hoover RN, et al. Mortality from solid tumors among workers in formaldehyde industries: an update of the NCI cohort. Am J Ind Med. 2013;56(9):1015–26.
Yu MC, Garabrant DH, Huang TB, Henderson BE. Occupational and other non-dietary risk factors for nasopharyngeal carcinoma in Guangzhou, China. Int J Cancer. 1990;45(6):1033–9.
Mirabelli MC, Hoppin JA, Tolbert PE, Herrick RF, Gnepp DR, Brann EA. Occupational exposure to chlorophenol and the risk of nasal and nasopharyngeal cancers among U.S. men aged 30 to 60. Am J Ind Med. 2000;37(5):532–41.
Vaughan TL, Stewart PA, Teschke K, Lynch CF, Swanson GM, Lyon JL, et al. Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma. Occup Environ Med. 2000;57(6):376–84.
Siew SS, Kauppinen T, Kyyrönen P, Heikkilä P, Pukkala E. Occupational exposure to wood dust and formaldehyde and risk of nasal, nasopharyngeal, and lung cancer among Finnish men. Cancer Manag Res. 2012;4:223–32.
Chen Y, Chang ET, Liu Q, Cai Y, Zhang Z, Chen G, et al. Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study. Cancer. 2021;127(15):2724–35.
International Agency for Research on Cancer. Chemical Agents and Related Occupations. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol 100F. Lyon: World Health Organization. 2012.
Chang ET, Ye W, Zeng YX, Adami HO. The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2021;30(6):1035–47.
E M, Yin J, Jin W, Mao Y, Wu Q, Qiu J. Wood dust exposure and risks of nasopharyngeal carcinoma: a meta-analysis. Eur J Public Health. 2020;30(4):817–22.
Malker HS, McLaughlin JK, Weiner JA, Silverman DT, Blot WJ, Ericsson JL, et al. Occupational risk factors for nasopharyngeal cancer in Sweden. Br J Ind Med. 1990;47(3):213–4.
Ekpanyaskul C, Sangrajrang S, Ekburanawat W, Brennan P, Mannetje A, Thetkathuek A, et al. Semi-quantitative exposure assessment of occupational exposure to wood dust and nasopharyngeal cancer risk. Asian Pac J Cancer Prev. 2015;16(10):4339–45.
Slack R, Young C, Rushton L, British Occupational Cancer Burden Study G. Occupational cancer in Britain. Nasopharynx and sinonasal cancers. Br J Cancer. 2012;107 Suppl 1:S49-S55.
Beigzadeh Z, Pourhassan B, Kalantary S, Golbabaei F. Occupational exposure to wood dust and risk of nasopharyngeal cancer: A systematic review and meta-analysis. Environ Res. 2019;171:170–6.
Zheng W, McLaughlin JK, Gao YT, Gao RN, Blot WJ. Occupational risks for nasopharyngeal cancer in Shanghai. J Occup Med. 1992;34(10):1004–7.
Li W, Ray RM, Gao DL, Fitzgibbons ED, Seixas NS, Camp JE, et al. Occupational risk factors for nasopharyngeal cancer among female textile workers in Shanghai, China. Occup Environ Med. 2006;63(1):39–44.
Talibov M, Auvinen A, Weiderpass E, Hansen J, Martinsen JI, Kjaerheim K, et al. Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population-based case-control study in four Nordic countries. Int J Cancer. 2017;141(6):1140–7.
Riska A, Martinsen JI, Kjaerheim K, Lynge E, Sparen P, Tryggvadottir L, et al. Occupation and risk of primary fallopian tube carcinoma in Nordic countries. Int J Cancer. 2012;131(1):186–92.
Hadkhale K, Martinsen JI, Weiderpass E, Kjaerheim K, Lynge E, Sparen P, et al. Occupation and Risk of bladder cancer in Nordic countries. J Occup Environ Med. 2016;58(8):e301-7.
Pukkala E, Martinsen JI, Lynge E, Gunnarsdottir HK, Sparén P, Tryggvadottir L, et al. Occupation and cancer - follow-up of 15 million people in five Nordic countries. Acta Oncol. 2009;48(5):646–790.
Pukkala E, Engholm G, Hojsgaard Schmidt LK, Storm H, Khan S, Lambe M, et al. Nordic Cancer Registries - an overview of their procedures and data comparability. Acta Oncol. 2018;57(4):440–55.
Barrett D, Ploner A, Chang ET, Liu Z, Zhang C-X, Liu Q, et al. Past and recent salted fish and preserved food intakes are weakly associated with nasopharyngeal carcinoma risk in adults in southern China. J Nutr. 2019;149(9):1596–605.
Zhong L, Goldberg MS, Gao YT, Jin F. Lung cancer and indoor air pollution arising from Chinese-style cooking among nonsmoking women living in Shanghai, China. Epidemiol. 1999;10(5):488–94.
He Y-Q, Xue W-Q, Shen G-P, Tang L-L, Zeng Y-X, Jia W-H. Household inhalants exposure and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China. BMC Cancer. 2015;15(1):1022.
Acquavella J, Olsen G, Cole P, Ireland B, Kaneene J, Schuman S, et al. Cancer among Farmers: A Meta-Analysis. Ann Epidemiol. 1998;8(1):64–74.
Lynge E, Andersen A, Rylander L, Tinnerberg H, Lindbohm ML, Pukkala E, et al. Cancer in persons working in dry cleaning in the Nordic countries. Environ Health Perspect. 2006;114(2):213–9.
Loomis D, Guha N, Hall AL, Straif K. Identifying occupational carcinogens: an update from the IARC Monographs. Occup Environ Med. 2018;75(8):593–603.
International Agency for Research on Cancer. Arsenic, metals, fibres and dusts. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 100C. Lyon: World Health Organization. 2012.
Reijula J, Kjaerheim K, Lynge E, Martinsen JI, Reijula K, Sparén P, et al. Cancer incidence among waiters: 45 years of follow-up in five Nordic countries. Scand J Public Health. 2015;43(2):204–11.
Yu IT, Chiu YL, Wong TW, Tang JL. Deaths from nasopharyngeal cancer among waiters and waitresses in Chinese restaurants. Int Arch Occup Environ Health. 2004;77(7):499–504.
Reijula J, Johnsson T, Kaleva S, Tuomi T, Reijula K. Total prohibition of smoking but not partial restriction effectively reduced exposure to tobacco smoke among restaurant workers in Finland. Int J Occup Med Environ Health. 2013;26(5):682–92.
Xue W-Q, Qin H-D, Ruan H-L, Shugart YY, Jia W-H. Quantitative association of tobacco smoking with the risk of nasopharyngeal carcinoma: a comprehensive meta-analysis of studies conducted between 1979 and 2011. Am. J. Epidemiol. 2013;178(3):325–38.
Long M, Fu Z, Li P, Nie Z. Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies. BMJ Open. 2017;7(10):e016582.
Ellingsen DG, Fladseth G, Daae HL, Gjølstad M, Kjaerheim K, Skogstad M, et al. Airborne exposure and biological monitoring of bar and restaurant workers before and after the introduction of a smoking ban. J Environ Monit. 2006;8(3):362–8.

Tables 1 and 2 are available in the Supplementary Files section.

No competing interests reported.

Download PDF

Editorial decision: Major revision
29 Aug, 2022
Reviews received at journal
25 Aug, 2022
Reviews received at journal
22 Jun, 2022
Reviewers agreed at journal
16 Jun, 2022
Reviewers agreed at journal
13 Jun, 2022
Reviewers invited by journal
10 Jun, 2022
Editor assigned by journal
10 Jun, 2022
Editor invited by journal
19 May, 2022
Submission checks completed at journal
19 May, 2022
First submitted to journal
09 May, 2022

You are reading this latest preprint version

Occupational risk variation of nasopharyngeal cancer in the Nordic countries

Status:

Version 1

Abstract

Background

Methods

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1