Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis
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)
- et al.
Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years
Food Chem Toxicol
(2009) - et al.
Guidelines for application of meta-analysis in environmental epidemiology. ISLI Risk Science Institute
Regul Toxicol Pharmacol
(1995) - et al.
Epidemiologic studies of chrome and cancer mortality: a series of meta-analyses
Regul Toxicol Pharmacol
(2005) - et al.
Epidemiology and prevention of oral cancer
Oral Oncol
(1997) Chromium
J Toxicol Clin Toxicol
(1999)- IARC. Monographs on the evaluation of carcinogenic risks to humans: chromium, nickel and welding. World Health...
Occupational exposure to hexavalent chromium; final rule
(2006)- et al.
Is hexavalent chromium carcinogenic via ingestion? A weight-of-evidence review
J Toxicol Environ Health A
(2002) Toxicological Review of Hexavalent Chromium
(1998)- Lucas JB, Kramkowski RS. Health hazard evaluation determination report number 74-87-221. Cincinnati, OH: US Department...
Occupational cancer and other health hazards in a chromate plant: a medical appraisal. II. Clinical and toxicologic aspects
Ind Med Surg
Cancer mortality in a Chinese population exposed to hexavalent chromium in drinking water
Epidemiology
Cancer mortality in chinese populations surrounding an alloy plant with chromium smelting operations
J Toxicol Environ Health A
Cancer mortality among arc welders exposed to fumes containing chromium and nickel. Results of a third follow-up: 1989–1995
J Occup Environ Med
Lung cancer among workers in chromium chemical production
Am J Ind Med
Lung cancer mortality among chromate production workers
Occup Environ Med
Carcinogenic hazards in the manufacture of chromium ferroalloys
Gig Tr Prof Zabol
Cancer mortality among workers in the Tuscan tanning industry
Br J Ind Med
Risk of lung cancer among masons in Iceland
Occup Environ Med
Mortality and incidence of tumours among ferrochromium workers
Br J Ind Med
Mortality study among workers producing chromate pigments in France
Int Arch Occup Environ Health
Lung cancer mortality in the German chromate industry, 1958 to 1998
J Occup Environ Med
Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification
Int Arch Occup Environ Health
Episheet software: spreadsheets for the analysis of epidemiologic data
Mortality among aircraft manufacturing workers
Occup Environ Med
Cancer mortality among workers exposed to zinc chromate paints
J Occup Med
Mortality among workers in the metal polishing and plating industry, 1951–1969
J Occup Med
Mortality from respiratory cancer and other causes in United Kingdom chromate production workers
Br J Ind Med
Mortality study among workers producing ferroalloys and stainless steel in France
Br J Ind Med
Risk of lung cancer among former chromium smelter workers
Am J Ind Med
Cited by (78)
Cancer mortality and chemical exposure in a retrospective zinc and lead smelter cohort: A 48-year follow-up
2022, International Journal of Hygiene and Environmental HealthChromium
2021, Handbook on the Toxicology of Metals: Fifth EditionEvaluating tissue levels of the eight trace elements and heavy metals among esophagus and gastric cancer patients: A comparison between cancerous and non-cancerous tissues
2021, Journal of Trace Elements in Medicine and BiologyOccupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects
2021, Regulatory Toxicology and PharmacologyCitation 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).
p62 functions as a signal hub in metal carcinogenesis
2021, Seminars in Cancer Biology