Send letter to journal:
Re: Author's reply to occupational exposures and pancreatic cancer: a meta-analysis

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.

Send letter to journal:
Re: Excess pancreatic cancer risk and exposure to nickel and nickel compounds

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 (Ojajärvi 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 Ojajärvi 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 Ojajärvi 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 Ojajärvi et al. analysis[1]:

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

* SMR/100 for cohort studies.

Combining the data from all of these studies with the meta-analysis random effects model employed by Ojajärvi 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 Ojajärvi 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 even the lower 95% confidence limit for the Ojajärvi et al.[1] MRR (1.2).

The fact that the Ojajärvi 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 Ojajärvi 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 Ojajärvi 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 Ojajärvi et al. analysis[1] call into question the veracity of a hypothesis that links nickel exposure to increased pancreatic cancer risk.

References

1 Ojajärvi 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.