Urinary Lead Concentration Is an Independent Predictor of Cancer Mortality in the U.S. General Population

Abstract

Lead is a ubiquitous pollutant that constitutes an environmental hazard worldwide. Although lead has been known as a carcinogenic factor in animal models, its role in human carcinogenesis is still a topic of debate with limited epidemiological evidence. Moreover, the association between urinary lead, as the most non-invasive and accessible way for lead measurement in human, and cancer mortality in general population has never been explored. We addressed this subject using continuous National Health and Nutrition Examination Survey 1999–2010 data and its Mortality Follow-Up Study. Of 5,316 subjects in study population, 161 participants died due to cancer. Cancer-specific mortality was associated with urinary lead levels after multivariable adjustment. Kaplan–Meier survival curve and cubic regression spline analyses indicated that high concentration of urinary lead exhibited significant association with raised death rate of cancer. Despite the marked decrease in environmental lead levels over the past three decades, lead exposure is still the significant determinant of cancer mortality in general population in U.S., and quantification of urinary lead may serve as a non-invasive approach to facilitate biomarker discovery and clinical translational research.

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

“…[Pb] u may, thus, be used as a proxy for [Pb] p . The utility of urine in monitoring Pb exposure has been illustrated in studies in Japan [ 193 ], Belgium [ 194 ], China [ 195 ], Thailand [ 12 ] and the U.S. [ 196 ]. In a Chinese study, workers in a lead–zinc mine had higher [Pb] u , [Cd] u and urinary 8-hydroxydeoxyguanosine, an indicator of oxidative stress, compared with those who worked in a steel smelting plant [ 195 ].…”

“…This finding is reminiscent of studies relating E Cd to eGFR ( Section 4.3.2 ). In a follow-up study of 5316 participants in NHANES 1999–2010, [Pb] u levels > 1.26 μg/L were associated, respectively, with 1.79- and 6.60-fold increases in mortality from all causes and cancer [ 196 ].…”

“…In another follow-up of participants in the same cycle, [Pb] b 1.0–6.7 μg/dL was associated with 1.37-, 1.70- and 2.08-fold increases in death from all causes, CVD, and ischemic heart disease [ 321 ]. In the NHANES 1999–2010 follow-up study ( n = 5316), exposure to low levels of Pb, reflected by [Pb] u > 1.26 μg/dL, may increase the risk of deaths from all causes and cancer by 1.79- and 6.60-fold, respectively [ 196 ]. A 44% increase in CVD mortality was observed for every 10-fold increase in hematocrit-corrected [Pb] b in a follow-up of participants, aged ≥40 years, in NHANES 1999–2010 ( n = 18,602) [ 322 ].…”

Effects of lead and cadmium on the immune system and cancer progression

“…Regarding lead carcinogenesis, a study investigating the association between urinary lead and cancer mortality showed that urinary lead levels were predictive of cancer-related death [93]. In contrast, a previous case-control study found no evidence of an association between urinary lead concentrations and breast cancer risk [94].…”

Plasma concentration of cadmium, lead and chromium in smokers and nonsmokers in Tripoli, Libya: A comparative study

“…In case of Pb, human exposure occurs through ingestion or inhalation [14], it accumulates in bones and teeth [15] while excreted through the feces and also in the urine [16]. The half-life of lead, which is stored in bones, could be up to nearly 48 years, reflecting that it has a long-term effects on health [17]. Pb is considered as a carcinogen [18] and numerous studies have pointed out it is associated with hypertension [19], chronic kidney disease [20] cognitive and neuromuscular decline [21].…”