Site-specific cancer risk following cobalt exposure via orthopedic implants or in occupational settings: A systematic review and meta-analysis.

In 2020, the European Commission up-classified metal cobalt as Class 1B Carcinogen (presumed to have carcinogenic potential) based primarily on data from rodent inhalation carcinogenicity studies. This up-classification requires an assessment under the Medical Device Regulations of cobalt cancer risk from medical devices. We performed a systematic review and meta-analysis to evaluate site-specific cancer risks with cobalt exposure from either total joint replacement (TJR) or occupational exposure (OC). Results were stratified by exposure type (OC or TJR), exposure level (metal-on-metal (MoM) or non-MoM), follow-up duration (latency period: <5, 5-10 or >10 years), and cancer incidence or mortality (detection bias assessment). From 30 studies (653,104 subjects, average 14.5 years follow-up), the association between TJR/OC and cancer risk was null for 22 of 27 cancer sites, negative for 3 sites, and positive for prostate cancer and myeloma. Significant heterogeneity and large estimate ranges were observed for many cancer sites. No significant increase in estimates was observed by exposure level or follow-up duration. The current evidence, including weak associations, heterogeneity across studies and no increased association with exposure level or follow-up duration, is insufficient to conclude that there exists an increased risk for people exposed to cobalt in TJR/OC of developing site-specific cancers.

Carcinogenic assessment of cobalt-containing alloys in medical devices or cobalt in occupational settings: A systematic review and meta-analysis of overall cancer risk from published epidemiologic studies.

In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review. We performed a systematic review and meta-analysis of published, peer-reviewed epidemiologic studies evaluating the association between overall cancer risk and exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings. Study-specific estimates were pooled using random-effects models. Analyses included 20 papers on orthopedic implants and 10 occupational cohort papers (~1 million individuals). The meta-analysis summary estimates (95% confidence intervals) for overall cancer risk were 1.00 (0.96-1.04) overall and 0.97 (0.94-1.00) among high-quality studies. Results were also similar in analyses stratified by type of exposure/data sources (occupational cohort, implant registry or database), comparators (general or implant population), cancer incidence or mortality, follow-up duration (latency period), and study precision. In conclusion, meta-analysis found no association between exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings and overall cancer risk, including an analysis of studies directly comparing metal-on-metal vs. non-metal-on-metal implants.

An Ecological Evaluation of Vinyl Chloride Exposure and Liver Cancer Incidence and Mortality in Texas.

The goal of this analysis was to evaluate the association between county-level ambient vinyl chloride (VC) and county-level liver cancer incidence and mortality rates in Texas. Modeled county-level ambient VC data were obtained from the National Air Toxics Assessment. Age-adjusted county-level liver cancer incidence rates were abstracted from the Texas Cancer Registry and age-standardized county-level liver cancer mortality rates were obtained from the peer-reviewed literature. Multivariable imputation was utilized to impute incidence rates in counties with suppressed liver cancer incidence rates. Negative binomial and Poisson regression models were utilized to evaluate the association between county-level ambient VC and county-level liver cancer incidence and mortality rates, respectively, adjusted for county-level heavy drinking prevalence, hepatitis mortality rates, median income, and race (percent Hispanic). County-level ambient VC was not associated with county-level liver cancer incidence or mortality rates. Specifically, when compared to the lowest tertile of ambient VC, the middle (relative risk [RR]: 1.06, 95% confidence interval [CI]: 0.95-1.19) and highest (RR: 1.03, 95% CI: 0.90-1.17) tertiles of ambient VC were not associated with liver cancer incidence. Similarly, county-level ambient VC in the middle (RR: 0.95, 95% CI: 0.85-1.05) and highest (RR: 0.93, 95% CI: 0.82-1.05) tertiles were not associated with liver cancer mortality. This analysis suggests that county-level ambient VC is not associated with liver cancer incidence or mortality in Texas. Our study provides novel results regarding liver cancer risk from low-level non-occupational exposure to ambient VC.