Lead and cancer: a narrative review and risk of bias assessment (2003–2020)

Lead exposure may contribute to harmful human health effects, but evidence of its carcinogenicity is limited. The International Agency for Research on Cancer (IARC) in 2006 classified lead as "probably carcinogenic" (Group 2A), based on limited evidence in humans and sufficient evidence in animals. To further synthesize evidence on lead's carcinogenicity, this review included a literature search and risk of bias assessment of 43 peer-reviewed epidemiological studies on lead exposure and cancer outcomes published between 2003 and 2020. Using the National Toxicology Program's Office of Health Assessment and Translation Risk of Bias approach, 13 Tier One studies (primarily low risk) and 30 Tier Two studies (low and high risk) were identified. These studies characterized lead exposure through biologic media (i.e., blood, urine, tissues, hair, nails), and/or work histories, and evaluated cancers of the biliary tract, brain and central nervous system, breast, digestive tract, head and neck, blood, mesothelium, reproductive organs, respiratory tract, skin, thyroid, and urinary tract. Notably, breast, thyroid, and head and neck cancers were not previously included in the IARC 2006 monograph. Across all site-specific cancers examined, at least one study reported an association with lead exposure except for skin cancer. Respiratory tract cancers had the most epidemiologic studies showing positive associations with lead exposure. Study limitations were commonly tied to risk of bias for confounding, exposure characterization, and outcome assessments. Taken together, future studies would benefit from robust experimental designs with thorough adjustments for confounders, large diverse populations, and standardized exposure assessments particularly for cancers with limited data.