Elsevier

Cancer Epidemiology

Volume 34, Issue 4, August 2010, Pages 388-399
Cancer Epidemiology

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

https://doi.org/10.1016/j.canep.2010.03.013Get rights and content

Abstract

Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI = 0.77–1.34)]; esophagus [1.17 (95% CI = 0.90–1.51)]; stomach [1.09 (95% CI = 0.93–1.28)]; colon [0.89 (95% CI = 0.70–1.12)]; and rectum [1.17 (95% CI = 0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR = 1.49 (95% CI = 1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.

Introduction

Inhalation exposure to hexavalent chromium [Cr(VI)] in certain occupations has been associated with an increased risk of lung cancer, yet increases in cancer risk outside the respiratory tract have not been reported consistently. Cancer risk assessment for Cr(VI) has traditionally addressed only inhalation exposures [1], [2], [3], [4], [5]. However, the observation in a recent National Toxicology Program (NTP) study of increased rates of oral-cavity tumors in rats and small intestine tumors in mice administered Cr(VI) in drinking water at concentrations ranging from 20 to 180 mg/L [6] suggests that an increased risk of gastrointestinal (GI) tract cancers may exist among humans exposed to Cr(VI). Whether Cr(VI) poses a cancer hazard from ingestion exposures in humans is an important public health question because a substantial proportion of the public is routinely exposed to low levels of Cr(VI) in drinking water. For example, low levels of Cr(VI) exist in at least one-third of California's drinking-water supply [6]. An important consideration in cancer risk assessment is whether cancers observed in rodents are relevant to human exposures, and epidemiologic findings for GI cancers among Cr(VI)-exposed workers can contribute to a weight of evidence (WOE) analysis for cancer risk assessment.

Epidemiologic data from numerous studies of occupationally exposed cohorts are available to evaluate the association between Cr(VI) and GI tract cancers in humans. Although occupational exposures mostly occur by inhalation, breathing in Cr(VI) could expose tissues in the GI tract due to oral respiration and redistribution of inhaled particulates from the respiratory tract to the GI tract. GI effects including stomach ulcers and distress have been reported among Cr(VI) exposed workers suggesting that occupational exposure can result in exposure to the GI tract [7], [8]. Also, if the reductive capacity of the stomach is overwhelmed by very high levels of Cr(VI) exposure, ingested Cr(VI) might pass from the stomach to the small intestine, and although less likely, to the colon and rectum. An increase in stomach cancer mortality was reported in an ecologic study of villagers exposed to Cr(VI) in drinking water in China [9], while an additional analysis of the same data concluded that there was no exposure–response relationship between Cr(VI) in drinking water and stomach, lung or all cancer mortality [10].

The objectives of this study are to:

  • 1.

    Systematically review the epidemiologic literature examining GI tract cancers (oral, esophageal, stomach, small intestine, colon, and rectal) among workers with known occupational exposures to Cr(VI).

  • 2.

    Conduct meta-analyses of studies of GI tract cancers identified by the literature search that meet specific inclusion criteria.

  • 3.

    Provide information to contribute to a WOE-based cancer risk assessment for GI tract cancers among Cr(VI)-exposed humans.

Section snippets

Literature search methods

Using the PubMed database, studies were identified that evaluated the relationship between Cr(VI) exposure and GI cancers, which were published between January 1, 1950 and December 1, 2009 in English or another language. A comprehensive search of the literature was conducted using terms including “chromium,” “hexavalent,” “chromate,” “chromic,” “chrome,” “occupation,” “cancer,” “neoplasm,” and “malignancy,” and terms for the specific GI cancer sites, with various combinations of “AND” and “OR”

Results

While more than 100 epidemiologic studies of Cr(VI)-exposed workers were initially identified by our literature search, the majority were focused on lung cancer and did not report incidence or mortality of GI tract cancers. Thirty-two studies, including four PMR studies, reported risk estimates for at least one of the individual GI cancers and met inclusion criteria (Table 1). Several studies reported risk estimates for a more highly exposed subcohort; one study [11] reported separate risk

Discussion

No study among the 32 included in this meta-analysis that evaluated cancer risk from occupational exposure to Cr(VI) reported statistically significant increases in oral cavity, colon, or rectal cancer. None of the meta-SMRs calculated for these GI cancers were significantly elevated, even when more highly exposed subcohorts were included in calculations. For esophageal and stomach cancer, statistically significant increases in risk were reported individually in a PMR analysis of deaths among

Conflict of interest

The authors have no conflicts to disclose.

Acknowledgements

This study was sponsored by Tierra Solutions, Inc., an affiliate of Maxus Energy Corporation. Tierra Solutions, Inc. manages and implements environmental investigation and remediation activities associated with properties formerly operated by the Diamond Shamrock Chemicals Company.

References (60)

  • T.F. Mancuso et al.

    Occupational cancer and other health hazards in a chromate plant: a medical appraisal. II. Clinical and toxicologic aspects

    Ind Med Surg

    (1951)
  • J.J. Beaumont et al.

    Cancer mortality in a Chinese population exposed to hexavalent chromium in drinking water

    Epidemiology

    (2008)
  • B.D. Kerger et al.

    Cancer mortality in chinese populations surrounding an alloy plant with chromium smelting operations

    J Toxicol Environ Health A

    (2009)
  • N. Becker

    Cancer mortality among arc welders exposed to fumes containing chromium and nickel. Results of a third follow-up: 1989–1995

    J Occup Environ Med

    (1999)
  • H.J. Gibb et al.

    Lung cancer among workers in chromium chemical production

    Am J Ind Med

    (2000)
  • R.S. Luippold et al.

    Lung cancer mortality among chromate production workers

    Occup Environ Med

    (2003)
  • L.V. Pokrovskaia et al.

    Carcinogenic hazards in the manufacture of chromium ferroalloys

    Gig Tr Prof Zabol

    (1973)
  • A.S. Costantini et al.

    Cancer mortality among workers in the Tuscan tanning industry

    Br J Ind Med

    (1989)
  • V. Rafnsson et al.

    Risk of lung cancer among masons in Iceland

    Occup Environ Med

    (1997)
  • G. Axelsson et al.

    Mortality and incidence of tumours among ferrochromium workers

    Br J Ind Med

    (1980)
  • F. Deschamps et al.

    Mortality study among workers producing chromate pigments in France

    Int Arch Occup Environ Health

    (1995)
  • T. Birk et al.

    Lung cancer mortality in the German chromate industry, 1958 to 1998

    J Occup Environ Med

    (2006)
  • U. Korallus et al.

    Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification

    Int Arch Occup Environ Health

    (1993)
  • T. Andersson et al.

    Episheet software: spreadsheets for the analysis of epidemiologic data

    (2004)
  • J.D. Boice et al.

    Mortality among aircraft manufacturing workers

    Occup Environ Med

    (1999)
  • N.A. Dalager et al.

    Cancer mortality among workers exposed to zinc chromate paints

    J Occup Med

    (1980)
  • A. Blair

    Mortality among workers in the metal polishing and plating industry, 1951–1969

    J Occup Med

    (1980)
  • J.M. Davies et al.

    Mortality from respiratory cancer and other causes in United Kingdom chromate production workers

    Br J Ind Med

    (1991)
  • J.J. Moulin et al.

    Mortality study among workers producing ferroalloys and stainless steel in France

    Br J Ind Med

    (1990)
  • K.D. Rosenman et al.

    Risk of lung cancer among former chromium smelter workers

    Am J Ind Med

    (1996)
  • Cited by (78)

    • Chromium

      2021, Handbook on the Toxicology of Metals: Fifth Edition
    • Occupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects

      2021, Regulatory Toxicology and Pharmacology
      Citation Excerpt :

      Based on the available data, the international agencies are of the opinion that there is no evidence for a greater risk of cancer in the digestive tract as a result of occupational exposure (ATSDR, 2012; ECHA, 2013b; IARC, 1990; IARC, 2012; NIOSH, 2013). Regarding cancer of the oral cavity, the ATSDR mentions the meta-analysis by Gatto et al. (2010). The meta-SMR for cancer in the oral cavity found in this study was 1.02 (95% CI 0.77–1.34) (ATSDR, 2012; Gatto et al., 2010).

    View all citing articles on Scopus
    View full text