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Article of the Week: Occupational variation in the incidence of testicular cancer in the Nordic countries

Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Time trends and occupational variation in the incidence of testicular cancer in the Nordic countries

Outi Ylönen*, Sirkku Jyrkkiö, Eero Pukkala§, Kari Syvanen and Peter J. Bostrom

*South-Karelian Central Hospital, University Hospital of Turku, Lappeenranta, Finland, Department of Oncology, ¶Department of Urology, University Hospital of Turku, Turku, Finland, School of Health Sciences, University of Tampere, Tampere, Finland and §Finnish Cancer Registry, Helsinki, Finland

 

Abstract

Objective

To describe the trends and occupational variation in the incidence of testicular cancer in the Nordic countries utilising national cancer registries, NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic Occupational Cancer) databases.

Patients and Methods

We obtained the incidence data of testicular cancer for 5‐year periods from 1960–1964 to 2000–2014 and for 5‐year age‐groups from the NORDCAN database. Morphological data on incident cases of seminoma and non‐seminoma were obtained from national cancer registries. Age‐standardised incidence rates (ASR) were calculated per 100 000 person‐years (World Standard). Regression analysis was used to evaluate the annual change in the incidence of testicular cancer in each of the Nordic countries. The risk of testicular cancer in different professions was described based on NOCCA information and expressed as standardised incidence ratios (SIRs)

Fig. 2. Testicular cancer incidence time trends by age in the Nordic countries 1960-2014 (5-year floating averages).

Results

During 2010–2014 the ASR for testicular cancer varied from 11.3 in Norway to 5.8 in Finland. Until 1998, the incidence was highest in Denmark. There has not been an increase in Denmark and Iceland since the 1990s, whilst the incidence is still strongly increasing in Norway, Sweden, and Finland. There were no remarkable changes in the ratio of seminoma and non‐seminoma incidences during the past 50 years. There was no increase in the incidences in children and those of pension age. The highest significant excess risks of testicular seminoma were found in physicians (SIR 1.48, 95% confidence interval [CI] 1.07–1.99), artistic workers (SIR 1.47, 95% CI 1.06–1.99) and religious workers etc. (SIR 1.33, 95% CI 1.14–1.56). The lowest SIRs of testicular seminoma were seen amongst cooks and stewards (SIR 0.56, 95% CI 0.29–0.98), and forestry workers (SIR 0.64, 95% CI 0.47–0.86). The occupational category of administrators was the only one with a significantly elevated SIR for testicular non‐seminoma (SIR 1.21, 95% CI 1.04–1.42). The only SIRs significantly <1.0 were seen amongst engine operators (SIR 0.60, 95% CI 0.41–0.84) and public safety workers (SIR 0.67, 95% CI 0.43–0.99).

Conclusions

There have always been differences in the incidence of testicular cancer between the Nordic countries. There is also some divergence in the incidences in different age groups and in the trends of the incidence. The effect of occupation‐related factors on incidence of testicular cancer is only moderate. Our study describes the differences, but provides no explanation for this variation.

Editorial: Occupational exposure and risk of testicular cancer: what can an ecological study in the Nordic countries tell us?

Examining the association between occupational exposure and incidence rates of testicular cancer over time in several countries may provide useful insights into the relative importance of lifestyle and environmental risk factors. The study by Ylonen et al. [1] assessed an ecological, rather than biological, effect of occupational exposure in order to understand differences in testicular cancer rates among populations; therefore, the authors could not draw causal inferences about the effect of occupational exposure on testicular cancer at the individual level [2]. Ecological studies are, however, a way of performing hypothesis‐generating population‐based research. They take advantage of the natural experiment following the changes in occupational exposure across countries [3].

Keeping the strengths and limitations of an ecological study design in mind, we should consider what can we learn from the study by Ylonen et al. [1]. Firstly, it is interesting to note that the authors themselves state in their discussion that ‘occupational exposure is probably not relevant’ for testicular cancer because the disease ‘is mainly diagnosed in young adults and the duration of occupational exposure before cancer diagnosis is short’. This highlights the fact that occupational exposure should probably be considered here as a proxy variable for other risk factors of testicular cancer: environmental exposure, physical activity, education, etc. This large study based on linkages of high‐quality data registers therefore merely aims to generate hypotheses. No clear patterns were observed, however, and future studies may benefit from similar ecological approaches using risk factors with a better rationale in the context of the aetiology of testicular cancer, such as socio‐economic statuts, diet or body mass index.

Secondly, the authors also note that this lack of unambiguous risk determinants and underlying mechanisms of testicular cancer makes it difficult to explain the geographic and temporal variations observed [1]. As the study did not have a hypothesis a priori, we find ourselves in a situation where occupational exposure may not be the best risk factor to examine in relation to risk of testicular cancer in an ecological study. The rationale for choosing occupational exposure as the risk factor is weak, and perhaps the authors would have been able to observe more clear patterns if they had conducted the study to assess bladder cancer, for which occupation has been a much more established risk factor and time to exposure has been found to be more relevant.

Thirdly, a clinical understanding of testicular cancer detection may inform changes in incidence over time and between countries. No additional information was provided by the authors, but changes in raising awareness of potential symptoms may have resulted in an increased incidence in a specific age group and/or country. Moreover, it would be of interest to know about differences among countries in terms of occupational exposure groups as this may also explain some of the patterns observed. A further assessment of the characteristics of different categories of occupational exposure could inform the patterns observed in this study and may shed light on the aetiology of testicular cancer.

In conclusion, ecological studies force us to think carefully about patterns of cancer incidence over time and among countries. Unfortunately, the findings cannot always lead to further hypotheses and careful consideration about potential risk factors needs to occur before conducting analyses. Moreover, detailed (clinical) knowledge is required about changes in diagnostic activity over time as well as potential changes in risk factor exposure. Future ecological studies using highly valuable resources, such as those used by Ylonen et al. [1] can help us understand cancer aetiology and prevention in more detail. They can be considered as a natural experiment to fill the gap in our understanding of the link between potential risk factors and risk of developing cancer.

Mieke Van Hemelrijck
Translational Oncology & Urology Research, Kings College
London, London, UK

 

References

1 Ylonen O, Jyrkkio S, Pukkala E, Syvanen K, Bostrom P. Time trends and occupational variation in the incidence of testicular cancer in the Nordic countries. BJU Int 2018; 122: 384–93

2 Morgenstern H. Ecologic studies. In Rothman K, Greenland S eds, Modern Epidemiology, 2nd edn, Philadelphia, PA: Lippincott Williams &Wilkins, 1998: 511–31

3 Sedgwick P. Ecological studies: advantages and disadvantages. BMJ 2014; 348: g2979

 

Editorial: Human development and its impact on genitourinary cancers

Using the extensive data from the WHO International Agency for Research on Cancer and the United Nations Human Development Report, Greiman et al. [1] aimed to investigate how human development is associated with incidence and mortality of genitourinary cancers. Even though they generate some interesting descriptive findings, we have to remain critical of these descriptive statistics and carefully assess what needs to be investigated next.

Firstly, despite having highlighted the need for attention to indicators of longevity, education, and income per head when assessing human development, the human development index (HDI) is a rather crude measurement. As a geometric mean of normalised indices for each of these three domains, the HDI simplifies but only captures part of what human development entails. Important indicators of health care such as inequalities, poverty, human security, and empowerment are not reflected in the HDI (www.hdr.undp.org). In the context of cancer incidence and mortality this is an important limitation, as it has for instance been shown that socioeconomic status affects early phase cancer trial referrals, which can be considered as a proxy for access to health care [2]. This inequality has been hypothesised to be linked to more comorbidities and lower education in those who are most deprived – a complex interaction which may not be completely captured by the HDI.

Secondly, registration of incidence and mortality of cancers may vary substantially between countries based on both medical practice and governance. These differences are important when trying to generate hypotheses following the ecological study of Greiman et al. [1]. In the case of bladder cancer, for instance, mortality has been estimated to be 17% in the Netherlands, compared to 22% in the USA, and 50% in the UK. As cancer treatments are expected to be similar in these developed countries, it has been thought that a lower registration of non-muscle-invasive bladder cancer in the UK could explain this higher proportion [3]. Thus, discrepancies in cancer registration, even between developed countries, may limit our awareness of cancer burden.

Thirdly, the study design suffers from ‘ecological fallacy’. The latter refers to the inability to draw causal inference about the effect of the HDI on genitourinary cancer at the individual level, in conjunction with the underlying problem of heterogeneity of exposure levels [4]. This limitation was not mentioned by Greiman et al. [1], but affects their conclusions. The lack of information on, for instance, smoking data, comorbidities, and ethnicity make it difficult to understand how development is affecting cancer incidence or mortality. It would have been interesting to also investigate cancers other than genitourinary cancers because a comparison of different tumour types might have shed light on differences in medical practice or risk factors across countries and help tease out the ecological effect of human development.

Despite the aforementioned limitations, the descriptive analysis by Greiman et al. [1] can be helpful for generating hypotheses – as also outlined by the authors. This ecological effect of human development on incidence and mortality rates of genitourinary cancers is particularly relevant when evaluating the impacts of prevention and intervention programmes for these cancers. Their findings suggest that further investigation is required to examine the hypothesis regarding human development and incidence/mortality of genitourinary cancers. To further elucidate this association, methodological challenges will need to be overcome, as HDI assessment has been criticised for being too crude. Nevertheless, it should be possible to collect more detailed information to allow for an understanding of which components of a country’s collective resources affect cancer incidence and mortality the most, e.g. differences in resources used for cancer detection and treatment.

Mieke Van Hemelrijck
Division of Cancer Studies, Translational Oncology and Urology Research (TOUR), Kings College London, London, UK

 

References

 

1 Greiman AKRosoff JSPrasad SM. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality. BJU Int2017; 120: 799-807

 

2 Mohd Noor A Sarker DVizor S et al. Effect of patient socioeconomic status on access to early-phase cancer trials. J Clin Oncol 2013; 31: 224– 30.

 

3 Boormans JLZwarthoff EC. Limited funds for bladder cancer research and what can we do about it. Bladder Cancer 2016; 2: 4951

 

4 Morgenstern H . Ecologic studies in epidemiology: concepts, principles, and methods. Annu Rev Public Health 1995; 16: 618

 

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