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• Excess pancreatic cancer risk and exposure to nickel and nickel compounds
  Steven K Seilkop
  Published on: 27 April 2016
• Author's reply to occupational exposures and pancreatic cancer: a meta-analysis
  Anneli Ojajarvi
  Published on: 27 April 2016

• Published on: 27 April 2016

  Excess pancreatic cancer risk and exposure to nickel and nickel compounds

  • Steven K Seilkop, Occupational Consultant

  Editor

  A meta-analysis that was recently published in this journal[1] suggested an association between excess pancreatic cancer risk and exposure to nickel and nickel compounds (meta-risk ratio = 1.9, 95% CI = 1.2 - 3.2, based on 4 studies). Through correspondence with the authors (Ojaj rvi et al.), I learned that their analysis excluded the many epidemiological studies that had been conducted on workers in the...

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  Editor

  A meta-analysis that was recently published in this journal[1] suggested an association between excess pancreatic cancer risk and exposure to nickel and nickel compounds (meta-risk ratio = 1.9, 95% CI = 1.2 - 3.2, based on 4 studies). Through correspondence with the authors (Ojaj rvi et al.), I learned that their analysis excluded the many epidemiological studies that had been conducted on workers in the nickel refining and alloy production industries. While most of these studies could not contribute to the meta-analysis due to a failure to specifically examine pancreatic cancer risk, I found two studies of nickel workers that provide relevant data.

  I believe that one of these studies, which examined mortality in 11,500 nickel mining and smelting workers,[2] should have been included in the Ojaj rvi et al. meta-analysis,[1] based on the criteria used for study selection. Another study of more than 30,000 workers exposed to nickel and nickel compounds in the production of nickel alloys[3] was published a few months after the May, 1998 cutoff that Ojaj rvi and coworkers utilized to establish the data base for their meta-analysis. The results from these studies[2][3] add substantially to data used in the Ojaj rvi et al. analysis[1]:

  Table 1 Cancer risks in studies of workers exposed to nickel and its compounds
  

  Study	Study Type	Included in Ojaj rvi et al.[1] ?	Pancreatic Cancer Deaths	Relative Risk*	95% Confidence Interval
  Thermoelectric Plant Workers 4]	Cohort	Yes	1	3.6	0.1 -19.9
  Cadmium/Nickel Battery Workers[5]	Cohort	Yes	3	1.7	0.3 4.9
  Los Angeles workplaces[6]	Case-control	Yes	6	1.5	0.4 5.7
  Montreal workplaces[7]	Case- Control	Yes	12	2.1	1.1 3.9
  Nickel mining and smelting workers[2]	Cohort	No	12	1.3	0.7 2.3
  Nickel alloy production workers[3]	Cohort	No	131	0.9	0.8 1.1

  * SMR/100 for cohort studies.

  Combining the data from all of these studies with the meta-analysis random effects model employed by Ojaj rvi et al.[1] produces a meta-risk ratio (MRR) of 1.3 (95% CI = 0.9 - 1.9). Interestingly, the two studies designed specifically to detect excess cancer risks associated with occupational nickel exposure[2][3] exhibit the lowest relative risks for pancreatic cancer and differ substantially from the MRR for nickel exposure calculated by Ojaj rvi et al. (1.9). Moreover, the estimated relative risk (0.9) from the study of nickel alloy workers[3] is significantly smaller (p<_0.05 than="than" even="even" the="the" lower="lower" _95="_95" confidence="confidence" limit="limit" for="for" ojaj="ojaj" rvi="ojaj rvi" et="et" al.1="al.1" mrr="mrr" _1.2.="_1.2." p="p"/> The fact that the Ojaj rvi et al.[1] MRR for nickel-related pancreatic cancer significantly overestimates the risk observed in a large cohort of nickel workers indicates that the authors' meta-analysis risk estimates should be viewed with an appropriate degree of caution. These meta-analysis results may be significantly biased because of limitations of the studies on which they are based. In studies that relate to nickel, the potential for misclassification bias is strong because of the complete confounding of nickel exposure with known carcinogenic hazards such as cadmium,[5] or asbestos, polycyclic aromatic hydrocarbons, chromium, beryllium, polychlorinated biphenyls, and hydrazine.[4] Similarly, the case-control study[7] that contributed the most substantial evidence of a nickel-related pancreatic cancer risk to the Ojavarvi et al. meta- analysis[1] provides equally strong statistical evidence of associations between excess pancreatic cancer and exposures to ten other substances, some of which are likely be correlated with occupational nickel exposure.

  While Ojaj rvi and coworkers are to be congratulated on their investigation of the aetiology of pancreatic cancer, it is my opinion that their results are most appropriately viewed as hypotheses that require further investigation, rather than compelling evidence that links substances to the induction of pancreatic cancer. As Ojaj rvi et al.[1] correctly suggest, research to test these hypotheses requires large studies and more refined measures of exposure. With respect to nickel and nickel compounds, data from large studies that were not included in the Ojaj rvi et al. analysis[1] call into question the veracity of a hypothesis that links nickel exposure to increased pancreatic cancer risk.

  References

  1 Ojaj rvi IA, Partanen TJ, Ahlbom A, et al. Occupational exposures and pancreatic cancer: a meta-analysis. Occ Environ Med 2000;97:316-324.

  2 Shannon HS, Walsh C, Jadon N, et al. Mortality of 11,500 nickel workers - extended follow up and relationship to environmental conditions. Toxicol Ind Health, 1988; 4:277-294.

  3 Arena VC, Sussman NB, Redmond CK, et al. Using alternative comparison populations to assess occupation-related mortality risk. J Occ Env Med 2000;40:907-916.

  4 Cammarano G, Crosignani P, Berrino H, et al. Additional follow-up of cancer mortality among workers in a thermoelectric power plant. Scand J Work Environ Health 1986;12:631-2.

  5 Andersson K, Elinder CG, Hogstedt C, et al. Mortality among cadmium and nickel-exposed workers in a Swedish battery factory. Curr Top Environ Toxicol Chem. 1985;8:399-408.

  6 Mack TM, Peters JM, Yu MC, et al. Pancreas cancer is unrelated to the workplace in Los Angeles. Am J Ind Med 1985;7:253-256.

  7 Siemiatycki J, Risk factors for cancer in the workplace, Boca Raton, FL: CRC Press, 1991.

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  Conflict of Interest:
  None declared.

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• Published on: 27 April 2016

  Author's reply to occupational exposures and pancreatic cancer: a meta-analysis

  • Anneli Ojajarvi
  • Other Contributors:
    • Timo Partanen

  Editor

  We thank Dr. Seilkop for his comment and have, in essence, not much to add to it. The study by Shannon et al.[1] had obviously been overlooked and the study by Arena et al.[2] was published after our deadline for the inclusion of studies.

  Dr. Seilkop´s Table has errors for the study by Andersson et al.[3] The number of pacreatic cancer deaths should be 2; relative risk should be 1.2; and 95% conf...

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  Editor

  We thank Dr. Seilkop for his comment and have, in essence, not much to add to it. The study by Shannon et al.[1] had obviously been overlooked and the study by Arena et al.[2] was published after our deadline for the inclusion of studies.

  Dr. Seilkop´s Table has errors for the study by Andersson et al.[3] The number of pacreatic cancer deaths should be 2; relative risk should be 1.2; and 95% confidence interval should be 0.1 - 4.5.

  References

  1. Shannon HS, Walsh C, Jadon N, et al. Mortality of 11,500 nickel workers - extended follow up and relationship to environmental conditions. Toxicol Ind Health 1991;7:277-94.

  2. Arena VC, Sussman NB, Redmond CK, et al. Using alternative comparison populations to assess occupation-related mortality risk. J Occup Environ Med 1998;40:907-16.

  3.Andersson VC, Elinder CG, Hogstedt C, et al. Mortality among cadmium and nickel-exposed workers in a Swedish battery factory. Current Topics in Environmental and Toxicological Chemmistry 1985;399-408.

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  Conflict of Interest:
  None declared.

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