JAMA Netw Open. 2026 May 1;9(5):e2614337. doi: 10.1001/jamanetworkopen.2026.14337.
ABSTRACT
IMPORTANCE: Urologic cancers have been linked to nonessential chemical elements with no known beneficial role in the body, though associations between low-level environmental exposure and urologic cancer risk are poorly understood.
OBJECTIVE: To systematically synthesize epidemiologic evidence on the association between environmental exposure to nonessential elements and risk of urologic cancers.
DATA SOURCES: English- and Chinese-language databases, including PubMed, Embase, Web of Science, Scopus, Cumulated Index in Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, and Wanfang, were searched from inception to January 27, 2026, without language restrictions.
STUDY SELECTION: Cohort and case-control studies reporting associations between exposure to at least 1 nonessential element (eg, arsenic, cadmium, lead, vanadium, or nickel) and risk of urologic cancers (prostate, bladder, kidney, urinary tract, or testicular) were included.
DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 4 author reviewers. Random-effects meta-analyses were conducted to estimate pooled relative risks (RRs) comparing the top vs bottom tertiles of exposure levels and to evaluate dose-response associations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.
MAIN OUTCOMES AND MEASURES: RRs for urologic cancers associated with exposure to nonessential elements.
RESULTS: Of 23 160 records screened, 68 studies met inclusion criteria and 62 were included in the meta-analysis. Comparing the top vs bottom tertile of exposure levels, pooled RRs for arsenic were 1.72 (95% CI, 1.33-2.22) for all urologic cancers, 1.60 (95% CI, 1.13-2.27) for bladder cancer, 1.19 (95% CI, 1.01-1.40) for prostate cancer, and 3.37 (95% CI, 1.71-6.66) for urothelial carcinoma (renal pelvis, ureter, urethra, and/or bladder). Arsenic exposure was not associated with kidney cancer (RR, 1.38; 95% CI, 0.76-2.52). A nonlinear dose-response association was observed between urologic cancer risk and drinking-water arsenic levels above 10 µg/L but not at or below this level; the RR steadily increased from concentrations of 10 to 429 µg/L. Estimated using the population attributable fraction, reducing arsenic concentrations in drinking water to 10 µg/L could potentially lower age-standardized annual rates of some urologic cancers by 0.1 to 31.8 cases per 100 000 population in high-exposure areas. Pooled RRs for overall urologic cancer risk were 1.38 (95% CI, 1.04-1.82) for top vs bottom tertile of cadmium exposure and 1.15 (95% CI, 1.05-1.26) for vanadium, whereas evidence for other elements was limited.
CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of epidemiologic studies, environmental exposure to arsenic, cadmium, and vanadium was associated with increased risk of urologic cancers, although high heterogeneity across studies limited interpretability. These findings highlight the need for high-quality prospective studies to assess causality and quantify the public health burden from environmental exposure to nonessential elements.
PMID:42172026 | DOI:10.1001/jamanetworkopen.2026.14337
