Occupational Asbestos Exposure and Kidney Cancer – A Causal Relationship?

Smith et al (1989) were among the first to posit that asbestos should be regarded as a ‘probable cause of human kidney cancer’ [interest was initially sparked in 1979 by Selikoff et al and Puntoni et al[i]].[ii] At the time, there were only a handful of human studies with ‘sufficient statistical power’ to infer excess kidney cancer mortality in asbestos-exposed workers, but their argument was intriguing regardless.

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[Source: Wikimedia Commons – BruceBlaus (19 June 2017) ‘A medical illustration depicting kidney cancer’]

Years later, in 2000, a systematic review and meta-analysis of cohort studies on occupational asbestos exposure and risk of kidney cancer was conducted by Sali and Boffetta.[iii]

In short, they found that, whilst it is unlikely that asbestos is responsible for an ‘important increase in kidney cancer risk’, high levels of exposure ‘might entail a small increase in risk’. The overall standard mortality ratio (SMR) of kidney cancer measured was only 1.1 (i.e. 10% more deaths than expected in the general population), but studies documenting elevated levels of exposure with higher SMR of lung cancer conveyed further increased the risk of kidney cancer.

Peters et al (2018) subsequently replicated this correlation in a large Canadian population-based control study, where 20% increased odds [odds ratio (OR) = 1.2] of kidney cancer experienced by ‘ever exposed’ to asbestos workers became higher as cumulative exposure and intensity of exposure escalated.[iv]

To-date, there is still limited information on the carcinogenicity of asbestos on non-respiratory organs, with the bulk of the epidemiological literature focusing on lung cancer, asbestosis, pleural thickening, mesothelioma and pleural plaques.

With this in mind, Boffetta and several of his University of Bologna peers recently revisited his earlier paper to complete an updated review. Their findings have since been published in the European Journal of Epidemiology.[v]

From a total of 927 publications (dated between 2001 and 2020), the group of Italian researchers eliminated duplicate studies, irrelevant studies and studies that did not meet the strict inclusion criteria. This left 13 post-2000 studies, whose results were combined with those of 29 publications formerly reviewed.

Ultimately, the results of this latest systematic review provide additional evidence to the hypothesis of a ‘lack of association between occupational asbestos exposure and risk of kidney cancer’, with the pooled analysis conveying a relative risk of 1.1 (as before, in 2000).

One of the possible explanations given for this outcome is that unlike mesothelioma, whose almost exclusive cause is contact with asbestos fibres, kidney cancer is associated with several (potentially coinciding) risk factors, which include, but are not limited to:

  • Genetic predisposition and family history of kidney cancer;
  • Lifestyle factors, e.g. physical inactivity, excessive alcohol consumption, smoking and poor dietary habits;
  • Exposure to a range of biological agents, e.g. solvents, pesticides, dusts, diesel and polycyclic aromatic hydrocarbons; and
  • Long-term, regular use of diuretic and analgesic medication, e.g. aspirin and ibuprofen.

Another explanation is that many studies do not specify in any particular detail the level or duration of individual exposures in a given industry or occupation. The data appears to be somewhat unreliable and is not conducive to dose-response assessment. Compounding these limitations is the fact that recorded cases of kidney cancer among asbestos-exposed workers are generally scarce and trends are much harder to distinguish when sample sizes are smaller. Longer-term follow up has been advocated as a means of overcoming the risk of missed kidney cancer detection. In the same way, there have been calls for forthcoming studies to be more restrictive in only evaluating participants with ‘probable or definite asbestos exposure’. The assumption is that  higher certainty in exposure status will increase the magnitude of association estimates.

Boffetta and colleagues are therefore adamant that it remains ‘controversial’ to cite a relationship between asbestos exposure and onset kidney cancer. Strength in this assertion has been bolstered still by consistent findings in a parallel systematic review and meta-analysis undertaken by Pang et al (2021), which failed to demonstrate evidence of a substantive association (neither kidney cancer mortality, nor incidence).[vi]

However, this is by no means a settled debate.

Indeed, there is some biological plausibility for a relationship rooted in animal studies – see Kanazawa et al (1970), who notably injected asbestos fibres subcutaneously into mice and acknowledged the migration of those fibres into the bloodstream and then onto the kidneys.[vii]

What is more, there have been some overwhelmingly strong findings that cannot help but pose a rebuttal to the presumption that there is no association. For instance, Mattioli et al (2002) exposed 7-fold odds (OR = 7.11) of renal cell carcinoma (the most common type of kidney cancer[viii]) for male asbestos-exposed workers in a hospital case-control study.[ix]

As discussed above, research validity often follows sample size. Incidentally, the largest study of kidney cancer in existence [Mandel et al (1995)[x]] calculated an odds ratio of 1.4 (40% more likely) for those ‘ever-exposed’ to asbestos, versus those ‘never-exposed’.

Perhaps the most contextually relevant research on health outcomes for UK workers was the British cohort study of Harding et al (2009), which also laid out evidence of a ‘statistically significant’ positive association between occupational asbestos exposure and the development of kidney cancer, with reference to a SMR of 1.52 (52% more deaths than expected).[xi]

Finally, there was the case report on a 76-year-old patient who presented to clinicians at the Scientific Institute of Pavia with ‘left flank pain’ after having been exposed to asbestos cement for a period of 7-years. It transpired that this pain was renal cell carcinoma.[xii] 1-year post-diagnosis (by which time his kidney had been surgically removed), the man subsequently developed fatal biphasic peritoneal mesothelioma and died 2-months later.

This was the second recorded case of renal cell carcinoma and peritoneal mesothelioma occurring in the same patient [the first was observed by Kawakita et al (1992)[xiii]], making it an ‘utterly exceptional’ case. Similarly, only 5 reports of renal cell carcinoma and pleural mesothelioma in the same patient were identified – see Sawazaki et al (2007)[xiv] and Bianchi et al (2007).[xv]

The infrequency of synchronous malignant mesothelioma and renal cell carcinoma was indicative of the fact that the pathogenic mechanism by which asbestos induces mesothelioma is distinct from that which induces carcinomas. Nonetheless, the prospect of both malignancies sharing some etiologic factors was not discounted, with history of asbestos exposure being the ‘most likely candidate’.

In simple terms, Lead Author and Pavia Institute Scholar, Stefano Candura, suggested that asbestos might be involved in the causation of both cancers, i.e. not a product of coincidence:

‘… there should be greater awareness that peritoneal mesothelioma and renal carcinoma may occur concurrently, though very rarely, and is an event with potential clinical and medical legal implications. The presence of MM may in fact prevent accurate recognition of the concomitant kidney neoplasm, and vice versa’.

Having underscored a genuine risk of asbestos-linked kidney cancer being underestimated worldwide, it is no wonder that academics frequently refer to the potential domino effect of establishing an association on asbestos-related disease claims.

For now, though, the quality of the available science is insufficient to point towards a causative link. Until this fact changes and literary improvements are recognised, any hypothetical claimant will struggle to make a compelling argument before a judge that their kidney cancer and/or mesothelioma was triggered by injurious asbestos exposure in a period of past employment

The Health and Safety Executive (HSE) is keeping tabs on this field of investigation (see Research Report 854[xvi]) and we will continue to do the same.

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[i] Selikoff IJ et al., Mortality experience of insulation workers in the United States and Canada, 1943—1976.  Ann N Y Acad Sci. 1979;330:91-116. ‘<https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1979.tb18711.x?sid=nlm%3Apubmed> accessed 2 September 2021.

Puntoni R et al., Mortality among shipyard workers in Genoa, Italy. Ann N Y Acad Sci. 1979;330:353-77. <https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1979.tb18738.x?sid=nlm%3Apubmed> accessed 2 September 2021.

Enterline PE et al., Asbestos and cancer: a cohort followed up to death. British Journal of Industrial Medicine 1987;44:396-401. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1007840/pdf/brjindmed00158-0036.pdf> accessed 2 September 2021.

[ii] Smith AH et al., Asbestos and kidney cancer: the evidence supports a causal association. Am J Ind Med. 1989;16(2):159-66. <https://pubmed.ncbi.nlm.nih.gov/2672801/> accessed 20 August 2021.

[iii] Sali D and Boffetta P, Kidney Cancer and Occupational Exposure to Asbestos: A Meta-Analysis of Occupational Cohort Studies. Cancer Causes Control. 2000 Jan;11(1):37-47. <https://www.jstor.org/stable/3553613> accessed 20 August 2021.

[iv] Peters CE et al., Workplace exposure to asbestos and the risk of kidney cancer in Canadian men. Can J Public Health. 2018 Aug; 109(4): 464–472. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182333/pdf/41997_2018_Article_95.pdf> accessed 20 August 2021.

[v] Zunarelli C et al., Occupational exposure to asbestos and risk of kidney cancer: an updated meta-analysis. Eur J Epidemiol. 2021 Jun 30. <https://link.springer.com/content/pdf/10.1007/s10654-021-00769-x.pdf> accessed 20 August 2021.

[vi] Pang CCY et al., Occupational Asbestos Exposure and Kidney Cancer: Systematic Review and Meta-analysis of Cohort Studies. Annals of Work Exposures and Health. Volume 65, Issue 3, April 2021, Pages 255–265 <https://academic.oup.com/annweh/article-pdf/65/3/255/37285403/wxaa114.pdf> accessed 20 August 2021.

[vii] Kanazawa K et al. Migration of asbestos fibres from subcutaneous injection sites in mice. Br J Cancer. 1970 Mar;24(1):96-106. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008534/pdf/brjcancer00466-0118.pdf> accessed 2 September 2021.

[viii] ‘Could asbestos exposure cause kidney cancer?’ (Asbestos Justice) <https://www.asbestosjustice.co.uk/asbestos-exposure-kidney-cancer/> accessed 20 August 2021.

[ix] Mattioli S et al., Occupational risk factors for renal cell cancer: a case--control study in northern Italy. J Occup Environ Med. 2002 Nov;44(11):1028-36.

[x] Mandel JS et al., International renal-cell cancer study. IV. Occupation. Int J Cancer. 1995 May 29;61(5):601-5. <https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.2910610503?sid=nlm%3Apubmed> accessed 2 September 2021.

[xi] Harding A-H et al., Mortality among British asbestos workers undergoing regular medical examinations (1971-2005). Occup Environ Med. 2009 Jul;66(7):487-95. <https://www.researchgate.net/profile/Damien-Mcelvenny-2/publication/24171296_Mortality_among_British_asbestos_workers_undergoing_regular_medical_examinations_1971-2005/links/0a85e53c3e9819bf28000000/Mortality-among-British-asbestos-workers-undergoing-regular-medical-examinations-1971-2005.pdf> accessed 2 September 2021.

[xii] Candura S et al., Renal cell carcinoma and malignant peritoneal mesothelioma after occupational asbestos exposure: case report. Med Lav. 2016 May 26;107(3):172-7. <https://www.mattioli1885journals.com/index.php/lamedicinadellavoro/article/download/4902/3920> accessed 20 August 2021.

Tim Povtak, ‘New Study: Asbestos Related to Most Common Kidney Cancer’ (1 July 2016 Asbestos.com)  <https://www.asbestos.com/news/2016/07/01/asbestos-related-kidney-cancer-renal-cell-carcinoma/> accessed 20 August 2021.

[xiii] Kawakita M et al., [Renal cell carcinoma with malignant peritoneal mesothelioma: report of a case] Hinyokika Kiyo. 1992 Aug;38(8):937-40. <https://pubmed.ncbi.nlm.nih.gov/1414743/> accessed 2 September 2021.

[xiv] Sawazaki H et al., [Renal cell carcinoma with malignant pleural mesothelioma after asbestos exposure: a case report]. Hinyokika Kiyo. 2007 Nov;53(11):805-8. <https://pubmed.ncbi.nlm.nih.gov/18051806/> accessed 2 September 2021.

[xv] Bianchi C et al., Malignant mesothelioma of the pleura and other malignancies in the same patient. Tumori. Jan-Feb 2007;93(1):19-22. <https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.653.3255&rep=rep1&type=pdf> accessed 2 September 2021.

[xvi] Slack R et al., The burden of occupational cancer in Great Britain: Kidney Cancer (2012 HSE) <https://www.hse.gov.uk/research/rrpdf/rr854.pdf> accessed 2 September 2021.