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Blood lead levels and bladder cancer among US participants: NHANES 1999鈥�2018

成人头条 volume听25, Article听number:听416 (2025) Cite this article

Abstract

Background and objectives

Pb (lead) is a heavy metal, its carcinogenicity for bladder cancer is still debated, the link between blood lead levels (BLLs) and bladder cancer was investigated in this study.

Methods

This cross-sectional study, using the NHANES (1999鈥�2018) database, explored the relationship between BLLs and bladder cancer among Americans aged 20鈥�85. It employed weighted multivariable logistic regression for analysis. Additionally, subgroup analyses and smoothed curve fitting were also performed.

Results

This study included a total of 40,486 participants, the body mass index (BMI) of the participants is 28.71鈥壜扁��6.68听kg/m2. The average BLL is 0.0858听渭mol/L (range: 0鈥�2.96听渭mol/L). A fully adjusted model showed that the BLL was associated with bladder cancer (odds ratio [OR]鈥�=鈥�2.946, 95% confidence interval [CI]鈥�=鈥�1.025 to 8.465, P鈥�=鈥�0.047) in people with BMI鈥�<鈥�28听kg/m2. However, no difference was found in the BMI鈥夆墺鈥�28听kg/m2 subgroup or in the general population. According to the subgroup analysis of participants with a BMI鈥�<鈥�28听kg/m2, blood lead was associated with bladder cancer in the male, nonhypertensive, and鈥�<鈥�70-year-old subgroups (p鈥�<鈥�0.05) but no significantly different is observed in other subgroups. In addition, we discovered a nonlinear association between the BLLs and bladder cancer risk using a linear regression model.

Conclusion

In this cross-sectional study, we found that the degree of correlation between BLLs and the risk of bladder cancer may vary among people with different BMIs. In people with BMI鈥�<鈥�28听kg/m2, a higher BLL was independently associated with bladder cancer. However, more experiments are needed to confirm this finding.

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Introduction

Pb (lead) is a heavy metal contaminant that can harm the human body. It is widely found in daily life, such as in mining, welding, batteries, making stained glass, and ceramics, especially in countries with low and middle incomes [1,2,3]. Lead is difficult to decompose and can be divided into organic and inorganic forms. It mainly enters the human body through digestion, respiration and skin processes [4]. The absorption rate can vary from 5.4鈥�48% according to the state of the exposed person [5] and the toxicity of lead depends on its chemical form, dosage and other factors [6]. A concentration of 0.242听渭mol/L for adults and 0.169听渭mol/L for children was defined as the reference value, but the threshold of harmful concentrations is not clear [7]. Lead affects cell metabolism by affecting antioxidant reactions, key enzymes and various hormone activities. Oxidative stress reactions caused by heavy metals can also cause cancer by interfering with DNA repair [8,9,10]. Recently, with the progress of social industrialization, human health has increasingly been affected by heavy metals [11].

Bladder cancer is the second most prevalent malignancy in the urinary system and ranks 10th in absolute incidence globally, with 549,000 new cases and approximately 200,000 deaths annually, making it the sixth most common cancer in the United States. Urothelial carcinoma is the main type of bladder cancer, accounting for more than 90% of bladder cancer cases. Among all cancers, bladder cancer has the highest lifetime treatment costs, with total annual treatment costs of approximately 鈧�3.6 billion in the United States and nearly 鈧�5 billion in Europe, adding to the burden on the global economy. Smoking is the strongest risk factor, but occupational and environmental toxins also significantly increase the disease burden of bladder cancer [12,13,14].

There are many reports about the harmful effects of lead on the human body, such as type 2 diabetes [15], urinary incontinence [16], hypertension [17, 18], cirrhosis of the liver [19], lung cancer [20], kidney function, neuropsychiatric problems and endocrine diseases [3, 21], but there are few reports about the correlation between lead and bladder cancer, and whether lead is a possible risk factor for bladder cancer is still under debate. This study aimed to reveal the link between lead and bladder cancer.

Methods

Study population

The NHANES is a nationally representative survey designed to assess the health and nutritional status of adults and children in the US. Participants underwent socioeconomic status assessment, dietary evaluation, medical and physiological examinations and laboratory tests. The database for this article is available from this website听(). We analyzed the data from the NHANES survey cycles (1999鈥�2018). In summary, the NHANES uses a sophisticated, multistage probability sampling method among civilians to examine a nationally representative sample. All participants completed questions about their health histories and demographics on household questionnaires that were provided by qualified investigators. Standardized medical examinations, blood sample collection, and other in-person testing at mobile examination facilities are also part of the research procedure. All NHANES participants provided informed consent. During the 1999鈥�2018 NHANES cycle, a total of 40,486 participants were included in the study. The recruitment process is illustrated in Fig.听1.

Fig.听1
figure 1

The flowchart for the participants. During the 1999鈥�2018 NHANES cycles, a total of 101,316 participants were involved. Of these, 25,555 lacked blood lead data, and 35,275 either had no cancer data or were afflicted with other cancers simultaneously. After excluding these participants, 40,486 were enrolled in this study, among whom 20,195 had a body mass index (BMI) lower than 28听kg/m2

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Study variable

Blood lead

Blood lead levels (BLLs) were analyzed at the Environmental Health Sciences Laboratory of the National Centre for Environmental Health (NCEH) and the Centre for Disease Control and Prevention (CDC). To measure BLLs, venous blood was collected. Before measurement, blood samples were weakened to a certain concentration and maintained at 鈭�20听掳C. The BLL was determined in the central laboratory using an Inductively Coupled Plasma Dynamic Reaction Cell Mass Spectrometer (ELAN DRC II, PerkinElmer, Norwalk) according to standard methodology. The lower limits of detection (LODs) for blood lead were different in each NHANES cycle and are presented in Table听1. The detection rate of blood lead for participants was 99.7%. All blood lead levels below the LOD were replaced with the LOD divided by the square root of 2. The specific laboratory method and other data can be obtained on the official website.

Table 1 The limit of detection (LOD) for lead in each NHANES cycle
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Bladder cancer

The answer to the question 鈥淓ver been told you had cancer or malignancy?鈥� on the MCQ questionnaire was used to determine whether the participants had cancer or malignancy. The answer to the question 鈥淲hat kind of cancer was it?鈥� was the location of the cancer.

Other clinical variables

Data on sex, age, race, education, marital status, the ratio of family income to poverty (PIR), alcohol consumption, BMI, high blood pressure, diabetes, creatinine level, and smoking status were also collected. Age, sex, race, education, marital status, and PIR can be obtained from demographic information (DEMO). Information on hypertension, diabetes, smoking status and drinking status can be obtained from the BPQ, DIQ, SMQ and ALQ questionnaires, respectively. Body mass index (BMI) data were obtained during the physical examination, and blood creatinine data were collected during the laboratory examination. More details of these covariate data can be found in听 The mean values are used when the covariates of continuous variables are missing (PIR 2.98, BMI 28.71听kg/m2, and blood creatine level 77.10听碌mol/L). The classification of all variables is shown in Table听2.

Table 2 Weighted characteristics of the study population based on serum lead
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Statistical analyses

The statistical analyses were conducted using R (version 3.4.3, ), Empower Stats software (), and Stata/MP16.0. Continuous variables are presented as the mean鈥壜扁�塻tandard deviation (SD), whereas categorical variables are presented as percentages. A linear regression model was used to analyze serial variables of baseline characteristics, and categorical variables were analyzed by the chi-square test. The participants were divided into quartiles by BLLs. Multivariate logistic regression models were used to investigate the associations between BLLs and bladder cancer incidence while adjusting for potential covariates. Three models were constructed: Model 1, an unadjusted model; Model 2, a partially adjusted model (adjusted for sex, age, race, education, marital status and PIR); and Model 3, a completely adjusted model (adjusted for sex, age, education, race, marital status and PIR, BMI, alcohol use, high blood pressure, diabetes status, creatinine level, and smoking status). BMI-stratified subgroup analysis was performed, and further stratified logistic regression analysis was conducted to clarify the correlation between the BLL and bladder cancer incidence. Multivariate tests were established by considering covariates and fitting a curve. Subgroup analyses were performed using logistic regression, and the participants were stratified by sex (male and female), age(<鈥�70听years and鈥�> =鈥�70听years), hypertension status (yes and no) and PIR (<鈥�2.5 and鈥�> =鈥�2.5) to explore the modification effect of these variables on the potential effect. This study incorporated the sampling weights recommended by NHANES in the analysis process to address the complexities of multi-stage cluster surveys. P鈥�<鈥�0.05 was considered to indicate statistical significance.

Results

Baseline characteristics

The baseline characteristics of the individuals according to blood lead level as a column-stratified variable are presented in Table听2. We studied a total of 40,486 individuals aged 20 to 85听years whose blood lead levels and bladder cancer status were measured. The average BLL is 0.0858听渭mol/L, range between 0 and 2.96听渭mol/L. Among all the participants, 48.77% were male, and the average age was 45.55鈥壜扁��16.37听years. The participants had an average BMI of 28.71听kg/m2, the gender ratio was roughly equal, and more than 50% of the participants were non-Hispanic white, had a high school education or more, and were married or living with a partner. Most people did not have high blood pressure or diabetes, but most people had a history of alcohol consumption, mostly moderate alcohol consumption. More than half of the participants were nonsmokers. A total of 0.17% of the participants (n鈥�=鈥�67) had bladder cancer.

The participants in the Quartile 4 group were generally older men. They had lower PIR and BMI, and higher creatinine levels. They were married or living with a partner, non-Hispanic white, heavy alcohol consumers, smokers, and without hypertension or diabetes. In addition, participants who were older, male, had a lower PIR and BMI, had a higher creatinine level, had a high school diploma or below, consumed heavy alcohol, were former or current smokers, had hypertension or had bladder cancer were more likely to have a higher blood lead level.

Associations between blood lead levels and bladder cancer

Table 3 displays the outcome of the multivariable regression analysis of the association between the BLL and bladder cancer incidence. In Model 1 without any adjustment, we identified a statistically significant correlation between increased BLLs and bladder cancer (OR 6.350, 95% CI 4.048, 9.961; P鈥�<鈥�0.001). With the increase of BLL, the risk of bladder cancer shows a significant upward trend (P for trend鈥�<鈥�0.001). The probability of having bladder cancer in the highest quartile was 16.387 times greater than that in the lowest quartile. However, after controlling for covariates, these associations were significantly weakened in Model 2 (OR 3.316, 95% CI 1.161, 9.437; P鈥�=鈥�0.027) and were no longer statistically significant in Model 3 (OR 2.280, 95% CI 0.575, 9.038; P鈥�=鈥�0.243). The average BMI of the total population in this study is 28.71听kg/m2. When adjusting for BMI鈥�<鈥�28听kg/m2 (n鈥�=鈥�20,195), univariate and multivariate analyses revealed that a high BLL was correlated with a greater chance of bladder cancer (n鈥�=鈥�41) in the raw model (OR 7.379, 95% CI 3.959, 13.751, P鈥�<鈥�0.001), model 2 (OR 3.649, 95% CI 1.380, 9.649, P鈥�=鈥�0.010), and model 3 (OR 2.946, 95% CI 1.025, 8.465, P鈥�=鈥�0.047). A correlation was not found when weighted multivariate logistic regression analysis was conducted in the BMI鈥夆墺鈥�28听kg/m2 group, suggesting that there are no potential modifiers in the relationship between BLLs and bladder cancer in the obese population (Tables听4 and 5).

Table 3 Association between blood lead levels (umol/L) and bladder cancer in the general population
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Table 4 Association between blood lead levels (umol/L) and bladder cancer in participants with BMI <28 kg/m2
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Table 5 Association between blood lead levels (umol/L) and bladder cancer in participants with BMI 鈮�28 kg/m2
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The weighted characteristics of the population with a BMI鈥�<鈥�28听kg/m2 are shown in Table听6.

Table 6 Weighted characteristics of the study population based on blood lead in participants with BMI鈥�<鈥�28听kg/m2
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Further subgroup analysis of participants with a BMI鈥�<鈥�28听kg/m2 was conducted, and the results are shown in Table听7. Blood lead levels were correlated with bladder cancer in males (P鈥�=鈥�0.01), those younger than 70听years (P鈥�<鈥�0.001), and those in the nonhypertensive subgroup (P鈥�=鈥�0.01) but were not significantly different from those in the other subgroups.

Table 7 Subgroup analyses of the association between blood lead and bladder cancer in participants with BMI鈥�<鈥�28听kg/m2
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The nonlinear relationship between BLLs and bladder cancer is presented in Figs.听2 and 3 as a curve. Figure听2 shows a nonlinear relationship between BLLs and bladder cancer in the general population. Adjusted variables: sex, age, race, education, marital status, PIR, BMI, alcohol status, high blood pressure, diabetes status, creatinine level, and smoking status. In people with a BMI鈥�<鈥�28听kg/m2, a clear increasing trend was detected, as shown in Fig.听3. Adjusted variables: age, sex, education, race, marital status, PIR, alcohol status, high blood pressure, diabetes status, creatinine level, and smoking status.

Fig.听2
figure 2

The association between BLL and bladder cancer in the general population. The red line represents the smooth curve fit between variables. The blue bands represent the 95% confidence intervals from the fits. Adjusted variables: age, sex, race, education, marital status, PIR, BMI, alcohol status, high blood pressure, diabetes status, creatinine level, and smoking status. PIR: Ratio of family income to poverty

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Fig.听3
figure 3

The association between BLL and bladder cancer stratified by BMI. The red line represents the smooth curve of participants with a BMI鈥�<鈥�28听kg/m2. The blue line represents the smooth curve of participants with a BMI鈥夆墺鈥�28听kg/m2. Adjusted variables: age, sex, race, education, marital status, PIR, alcohol status, high blood pressure, diabetes status, creatinine level, and smoking status. PIR: Ratio of family income to poverty

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Discussion

In this cross-sectional study from the NHANES 1999鈥�2018, there were differences in sex, age, education, PIR, BMI, creatinine levels, smoking, alcohol consumption and high blood pressure among different BLLs (p鈥�<鈥�0.001). The correlation between blood lead and blood pressure is consistent with the results reported by previous studies [17, 18]. A greater BLL was independently associated with bladder cancer in people with a BMI鈥�<鈥�28听kg/m2, the association is stable among those under 70听years old, without hypertension, and male, demonstrating that blood lead might be a contributing factor for bladder cancer.

Lead is a heavy metal with a broad occurrence. It can enter and accumulate in the human body in different ways. Accumulation in various organs can cause adverse reactions and may damage hematopoietic function, the nervous system, the cardiovascular system, the reproductive system, the urinary system, the digestive system, etc [15, 16, 18,19,20,21,22].听It can lead not only to neuropsychiatric diseases but also may lead to the progression of cancer [23].听Lead and its compounds have been classified as "probable" human carcinogens (Group 2A) by the International Agency for Research on Cancer (IARC) [24], There are numerous cross鈥攕ectional studies [25,26,27,28,29,30,31] and reviews [32, 33] indicating that lead may be associated with cancer. In addition Awadalla A et al. Compared the concentrations of cadmium (Cd) and lead (Pb) in 268 bladder cancer patients and 132 controls. It was found that the elevated blood Cd and Pb concentrations in bladder cancer patients were statistically significant, and the expression of miRNA鈥�21 in cancer tissues was significantly correlated with the blood Cd and Pb concentrations in bladder cancer patients [34] miRNA, short non鈥攃oding RNA, plays an important role in controlling differentiation, proliferation, apoptosis and autophagy. It is dysregulated in cancer through various mechanisms (amplification or deletion). Dysregulated miRNA can act as oncogene or tumor鈥攕uppressor gene in cancer, participate in cancer occurrence and metastasis, and is related to tumor status, grade, size, invasiveness and metastasis [35]. It also plays an important role in the malignant transformation of cells and tumorigenesis induced by specific chemical and metal carcinogens [36].

There are also articles suggesting that lead is not clearly associated with some cancers [37,38,39,40]. These studies are all characterized by large sample sizes, but none of them are related to bladder cancer. Whether lead can increase the risk of bladder cancer remains inconclusive.

The biological mechanisms underlying the relationship between lead exposure and bladder cancer are unknown. Apart from the miRNA鈥�21 we mentioned previously, there are several possible effects. The replacement of other ions, such as Ca2+, Mg2+, Fe2+ and Na+, interferes with cellular metabolism [8], which indirectly leads to an imbalance in antioxidant responses [41] that affects key enzymes and hormones [10]. In addition to direct damage, lead increases the levels of reactive oxygen species and calcium ions in cells, reduces the mitochondrial potential and reduces apoptosis through the release of cytochrome [42]. Continuous lead exposure may also affect immune function, which can induce cancer [43]. In addition, there are three additional carcinogenic mechanisms: the activation of redox-sensitive transcription factors, the activation of these transcription factors as mitotic signals, and the inhibition of DNA repair [9, 44].

Our study revealed that the BLLs was associated with bladder cancer in the general population, but the association became nonsignificant after accounting for covariates. In this study, the average BMI of the total population is 28.71听kg/m2. Given that 28听kg/m2is a relatively sensitive cut-off value for many diseases [45], hence, it is chosen as the cut-off value. Interestingly, blood lead was still found to be related to bladder cancer in people with a BMI鈥�<鈥�28听kg/m2, but not in the population with a BMI鈥夆墺鈥�28听kg/m2. Obesity is commonly regarded as risk factor for numerous cancers [46, 47]. However, there are also some studies indicating that obesity has a protective effect on cancer, this phenomenon is called the obesity paradox [48, 49]. Some scholars believe that selection bias, confounding factors, and using BMI as the sole criterion for measuring obesity while ignoring the independent roles of fat mass and lean body mass are possible reasons for the emergence of the obesity paradox [50, 51]. The cancer data in our study was obtained through questionnaires, and bias is inevitable. Moreover, the weight loss caused by cancer cachexia may lead to the occurrence of the obesity paradox. In addition, several studies have shown that BLL is negatively correlated with body weight [52], body fat content [53] and BMI [54], that is, the higher the BMI or body weight, the lower the BLL. The above explains the lack of statistical significance between BLL and bladder cancer for those with BMI鈥夆墺鈥�28听kg/m2, due to the interference of this group, the overall population also shows a lack of statistical significance in the relationship.

Our research has the following advantages. First, the reliability and representativeness of our study were enhanced, as the data were obtained from the NHANES with a large sample size, and covariates were considered to reduce confounding factors. Furthermore, our findings were validated by weighted multivariate logistic regression and subgroup analysis to determined the association between BLLs and bladder cancer among populations with different BMIs.

However, this investigation also has some limitations. This was a cross-sectional survey, and the data were obtained from an observational survey. It can only establish associations and not causation. Although efforts have been made to minimize confounding factors, there are still limitations, such as BLLs, which may not reflect the total amount of lead accumulated in the body. And in real settings, lead rarely exists alone and may coexist with other heavy metals it's hard to fully separate the influence of other heavy metals, potentially leading to inaccurate estimations of blood lead hazards. In addition, the exact mechanisms behind this positive relationship have not been well elucidated because the causes of bladder cancer are complex and influenced by various genetic and environmental factors, and some unobserved confounding factors or information was not collected in the survey. Further prospective studies are necessary in the future.

Conclusion

In conclusion, the risk of bladder cancer associated with BLLs varies among individuals with different BMIs. In the population with BMI鈥�<鈥�28听kg/m2, the risk of bladder cancer increases as the BLL rises, providing novel perspectives for future research. Because the findings were insufficient to show a causal association, more comprehensive prospective investigations are needed.

Data availability

The dataset supporting the conclusions of this article is available in the NHANES repository: .

References

  1. Mitra P, Sharma S, Purohit P, Sharma P. Clinical and molecular aspects of lead toxicity: An update. Crit Rev Clin Lab Sci. 2017;54(7鈥�8):506鈥�28.

    听 CAS听 听 听

  2. Obeng-Gyasi E. Sources of lead exposure in various countries. Rev Environ Health. 2019;34(1):25鈥�34.

    听 CAS听 听 听

  3. Walter K. What Is Lead Poisoning? JAMA. 2023;329(12):1040.

    听 听 听

  4. Fu Z, Xi S. The effects of heavy metals on human metabolism. Toxicol Mech Methods. 2020;30(3):167鈥�76.

    听 CAS听 听 听

  5. Rabinowitz MB, Kopple JD, Wetherill GW. Effect of food intake and fasting on gastrointestinal lead absorption in humans. Am J Clin Nutr. 1980;33(8):1784鈥�8.

    听 CAS听 听 听

  6. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Experientia Suppl. 2012;2012(101):133鈥�64.

    听 听

  7. Ruckart PZ, Jones RL, Courtney JG, et al. Update of the Blood Lead Reference Value - United States, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(43):1509鈥�12.

    听 CAS听 听 听 听

  8. Flora SJ, Mittal M, Mehta A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res. 2008;128(4):501鈥�23.

    CAS听 听 听

  9. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007;19(9):1807鈥�19.

    听 CAS听 听 听

  10. Dhir B, Sharmila P, Pardha Saradhi P, Sharma S, Kumar R, Mehta D. Heavy metal induced physiological alterations in Salvinia natans. Ecotoxicol Environ Saf. 2011;74(6):1678鈥�84.

    听 CAS听 听 听

  11. Rusyniak DE, Arroyo A, Acciani J, Froberg B, Kao L, Furbee B. Heavy metal poisoning: management of intoxication and antidotes. EXS. 2010;100:365鈥�96.

    CAS听 听 听

  12. Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of Bladder Cancer. Medical Sci (Basel, Switzerland). 2020;8(1):15.

    CAS听 听 听

  13. Comp茅rat E, Amin MB, Cathomas R, et al. Current best practice for bladder cancer: a narrative review of diagnostics and treatments. Lancet (London, England). 2022;400(10364):1712鈥�21.

    听 听 听

  14. Richters A, Aben KKH, Kiemeney L. The global burden of urinary bladder cancer: an update. World J Urol. 2020;38(8):1895鈥�904.

    听 听 听

  15. Zhu K, Zhang Y, Lu Q, et al. Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes. Environ Sci Pollut Res Int. 2022;29(51):76805鈥�15.

    听 CAS听 听 听

  16. Ni J, Li Z, Lu Y, et al. Relationship between exposure to cadmium, lead, and mercury and the occurrence of urinary incontinence in women. Environ Sci Pollut Res Int. 2022;29(45):68410鈥�21.

    听 CAS听 听 听

  17. Huang Z. Association Between Blood Lead Level With High Blood Pressure in US (NHANES 1999鈥�2018). Front Public Health. 2022;10:836357.

    听 听 听 听

  18. Tang J, Zhu Q, Xu Y, et al. Total arsenic, dimethylarsinic acid, lead, cadmium, total mercury, methylmercury and hypertension among Asian populations in the United States: NHANES 2011鈥�2018. Ecotoxicol Environ Saf. 2022;241:113776.

    听 CAS听 听 听

  19. Reja D, Makar M, Visaria A, Karanfilian B, Rustgi V. Blood lead level is associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A nationwide survey (NHANES 2011鈥�2016). Ann Hepatol. 2020;19(4):404鈥�10.

    听 CAS听 听 听

  20. Rhee J, Graubard BI, Purdue MP. Blood lead levels and lung cancer mortality: An updated analysis of NHANES II and III. Cancer Med. 2021;10(12):4066鈥�74.

    听 CAS听 听 听 听

  21. Qayyum S, Ara A, Usmani JA. Effect of nickel and chromium exposure on buccal cells of electroplaters. Toxicol Ind Health. 2012;28(1):74鈥�82.

    听 CAS听 听 听

  22. Rehman K, Fatima F, Waheed I, Akash MSH. Prevalence of exposure of heavy metals and their impact on health consequences. J Cell Biochem. 2018;119(1):157鈥�84.

    听 CAS听 听 听

  23. Ebrahimi M, Khalili N, Razi S, Keshavarz-Fathi M, Khalili N, Rezaei N. Effects of lead and cadmium on the immune system and cancer progression. J Environ Health Sci Eng. 2020;18(1):335鈥�43.

    听 CAS听 听 听 听

  24. Inorganic and organic lead compounds. IARC Monogr Eval Carcinog Risks Hum. 2006;87:1鈥�471.

    听

  25. Romaniuk A, Lyndin M, Sikora V, Lyndina Y, Romaniuk S, Sikora K. Heavy metals effect on breast cancer progression. J Occup Med Toxicol (London, England). 2017;12:32.

    听 听

  26. Basu S, Singh MK, Singh TB, Bhartiya SK, Singh SP, Shukla VK. Heavy and trace metals in carcinoma of the gallbladder. World J Surg. 2013;37(11):2641鈥�6.

    听 听 听

  27. Qayyum MA, Shah MH. Comparative assessment of selected metals in the scalp hair and nails of lung cancer patients and controls. Biol Trace Elem Res. 2014;158(3):305鈥�22.

    听 CAS听 听 听

  28. Qayyum MA, Shah MH. Comparative study of trace elements in blood, scalp hair and nails of prostate cancer patients in relation to healthy donors. Biol Trace Elem Res. 2014;162(1鈥�3):46鈥�57.

    听 CAS听 听 听

  29. Amaral AF, Porta M, Silverman DT, et al. Pancreatic cancer risk and levels of trace elements. Gut. 2012;61(11):1583鈥�8.

    听 CAS听 听 听

  30. Golabek T, Darewicz B, Borawska M, Markiewicz R, Socha K, Kudelski J. Lead concentration in the bladder tissue and blood of patients with bladder cancer. Scand J Urol Nephrol. 2009;43(6):467鈥�70.

    听 CAS听 听 听

  31. Chang CH, Liu CS, Liu HJ, et al. Association between levels of urinary heavy metals and increased risk of urothelial carcinoma. Int J Urol. 2016;23(3):233鈥�9.

    听 CAS听 听 听

  32. Furtak G, Koz艂owski M, Kwiatkowski S, Cymbaluk-P艂oska A. The Role of Lead and Cadmium in Gynecological Malignancies. Antioxidants (Basel, Switzerland). 2022;11(12):2468.

    CAS听 听 听 听

  33. Ahn J, Park MY, Kang MY, Shin IS, An S, Kim HR. Occupational Lead Exposure and Brain Tumors: Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2020;17(11):3975.

    听 CAS听 听 听 听

  34. Awadalla A, Mortada WI, Abol-Enein H, Shokeir AA. Correlation between blood levels of cadmium and lead and the expression of microRNA-21 in Egyptian bladder cancer patients. Heliyon. 2020;6(12):e05642.

    听 CAS听 听 听 听

  35. Liu X, Liu X, Wu Y, et al. MicroRNAs in biofluids are novel tools for bladder cancer screening. Oncotarget. 2017;8(19):32370鈥�9.

    听 听 听 听

  36. Humphries B, Wang Z, Yang C. The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis. Food Chem Toxicol. 2016;98(Pt A):58鈥�65.

    听 CAS听 听 听 听

  37. Wynant W, Siemiatycki J, Parent M, Rousseau MC. Occupational exposure to lead and lung cancer: results from two case-control studies in Montreal, Canada. Occup Environ Med. 2013;70(3):164鈥�70.

    听 听 听

  38. Gaudet MM, Deubler EL, Kelly RS, et al. Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts. Int J Cancer. 2019;144(5):1010鈥�6.

    听 CAS听 听 听

  39. Yan W, Liu X, Zhang G. Identification of potential food sources affecting blood lead levels and their health hazards (CVD, respiratory diseases, cancer). Sci Total Environ. 2024;906:167505.

    听 CAS听 听 听

  40. Callahan CL, Friesen MC, Locke SJ, et al. Case-control investigation of occupational lead exposure and kidney cancer. Occup Environ Med. 2019;76(7):433鈥�40.

    听 听 听

  41. Kasperczyk A, Machnik G, Dobrakowski M, Sypniewski D, Birkner E, Kasperczyk S. Gene expression and activity of antioxidant enzymes in the blood cells of workers who were occupationally exposed to lead. Toxicology. 2012;301(1鈥�3):79鈥�84.

    听 CAS听 听 听

  42. Moreira EG, Vassilieff I, Vassilieff VS. Developmental lead exposure: behavioral alterations in the short and long term. Neurotoxicol Teratol. 2001;23(5):489鈥�95.

    听 CAS听 听 听

  43. Metryka E, Chibowska K, Gutowska I, et al. Lead (Pb) Exposure Enhances Expression of Factors Associated with Inflammation. Int J Mol Sci. 2018;19(6):1813.

    听 听 听 听

  44. Silbergeld EK. Facilitative mechanisms of lead as a carcinogen. Mutat Res. 2003;533(1鈥�2):121鈥�33.

    听 CAS听 听 听

  45. Liu N, Birstler J, Venkatesh M, Hanrahan L, Chen G, Funk L. Obesity and BMI Cut Points for Associated Comorbidities: Electronic Health Record Study. J Med Internet Res. 2021;23(8):e24017.

    听 听 听 听

  46. Lengyel E, Makowski L, DiGiovanni J, Kolonin MG. Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors. Trends Cancer. 2018;4(5):374鈥�84.

    听 CAS听 听 听 听

  47. Parida S, Siddharth S, Sharma D. Adiponectin, Obesity, and Cancer: Clash of the Bigwigs in Health and Disease. Int J Mol Sci. 2019;20(10):2519.

    听 CAS听 听 听 听

  48. Li Y, Li C, Wu G, et al. The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis. Nutr Rev. 2022;80(7):1755鈥�68.

    听 听 听

  49. Petrelli F, Cortellini A, Indini A, et al. Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(3):e213520.

    听 听 听 听

  50. Lee DH, Giovannucci EL. The Obesity Paradox in Cancer: Epidemiologic Insights and Perspectives. Curr Nutr Rep. 2019;8(3):175鈥�81.

    听 听 听

  51. Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB. Obesity paradox in cancer: new insights provided by body composition. Am J Clin Nutr. 2014;99(5):999鈥�1005.

    听 CAS听 听 听

  52. Scinicariello F, Buser MC, Mevissen M, Portier CJ. Blood lead level association with lower body weight in NHANES 1999鈥�2006. Toxicol Appl Pharmacol. 2013;273(3):516鈥�23.

    听 CAS听 听 听 听

  53. Park S, Lee BK. Body fat percentage and hemoglobin levels are related to blood lead, cadmium, and mercury concentrations in a Korean Adult Population (KNHANES 2008鈥�2010). Biol Trace Elem Res. 2013;151(3):315鈥�23.

    听 CAS听 听 听

  54. Padilla MA, Elobeid M, Ruden DM, Allison DB. An examination of the association of selected toxic metals with total and central obesity indices: NHANES 99鈥�02. Int J Environ Res Public Health. 2010;7(9):3332鈥�47.

    听 CAS听 听 听 听

Acknowledgements

The authors would like to express their sincere gratitude to the staff and participants of the NHANES study. Without their dedication and contribution, this research would not have been possible.

Materials availability

Not applicable.

Code availability

Not applicable.

Funding

This work was supported by the Guangzhou Science and Technology Plan Project听[grant number 202201010834]; the Natural Science Foundation of Guangdong Province [grant number 2021A15010065]; the Guangzhou Health Science and Technology Project [grant number 20211A011103]; the Ministry of Education's Industry-University Cooperative Education Project in 2022 [grant number 220904082210823]; and the Doctoral Program of Guangdong Nature Foundation [grant number 2017A030310148],听The Key Clinical Specialty Project of Guangzhou Medical University (2020).听Guangzhou Medical Key Discipline(2021-2023,听2025-2027. The Key Clinical Specialty Project of Guangdong听Province (2022).

Author information

Author notes

  1. Mei Huang and Hongxiao Li contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, 621 Gangwan Road, Huangpu District, Guangzhou, Guangdong, 510700, China

    Mei Huang,听Hongxiao Li,听Jiahui Chen,听Liuqiang Li,听Yifei Zhan,听Yuxuan Du,听Jun Bian,听Meiling Chen听&听Dehui Lai

Authors
  1. Mei Huang

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  2. Hongxiao Li

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  4. Liuqiang Li

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  5. Yifei Zhan

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  6. Yuxuan Du

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  7. Jun Bian

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Contributions

M.H. (First Author):Writing鈥攐riginal draft, review & editing; H.L.(Co-first Author): Formal analysis, Methodology; J.C. and L.L. and Y.D.: Data curation; D.L. (Corresponding Author): Conceptualization, Funding Acquisition, Supervision; J.B. and M.C(Corresponding Author): Conceptualization, Supervision. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jun Bian, Meiling Chen or Dehui Lai.

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Ethics approval and consent to participate

The NCHS Research Ethics Review Board (ERB) approved the studies involving human participants. Informed consent was not required for this study in accordance with relevant national laws and institutional regulations.

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Not applicable.

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The authors declare no competing interests.

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Huang, M., Li, H., Chen, J. et al. Blood lead levels and bladder cancer among US participants: NHANES 1999鈥�2018. 成人头条 25, 416 (2025). https://doi.org/10.1186/s12889-025-21549-2

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  • DOI: https://doi.org/10.1186/s12889-025-21549-2

Keywords

成人头条

ISSN: 1471-2458

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