Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts

Gaudet, Mia M.; Deubler, Emily; Kelly, Rachel S.; Diver, W. Ryan; Teras, Lauren R.; Hodge, James; Levine, Keith; Haines, Laura G.; Lundh, Thomas; Lenner, Per; Palli, Domenico; Víneis, Paolo; Bergdahl, Ingvar A.; Gapstur, Susan M.; Kyrtopoulos, Soterios A.

doi:10.1002/ijc.31805

Cited by 42 publications

(8 citation statements)

References 44 publications

(80 reference statements)

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“…This may explain the conflicting results when different indicators of exposure were used. For instance, an association was not observed between breast cancer risk and [Cd] b [ 163 ], while [Cd] u has been consistently associated with a significant increase in risk for cancer [ 164 ].…”

Section: Dosimetry and Nephrotoxicity Assessmentmentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

107

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The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) to which most populations are exposed. Epidemiological studies examining the adverse effects of coexposure to Cd and Pb have shown that Pb may enhance the nephrotoxicity of Cd and vice versa. Herein, the existing tolerable intake levels of Cd and Pb are discussed together with the conventional urinary Cd threshold limit of 5.24 μg/g creatinine. Dietary sources of Cd and Pb and the intake levels reported for average consumers in the U.S., Spain, Korea, Germany and China are summarized. The utility of urine, whole blood, plasma/serum, and erythrocytes to quantify exposure levels of Cd and Pb are discussed. Epidemiological studies that linked one of these measurements to risks of chronic kidney disease (CKD) and mortality from common ailments are reviewed. A Cd intake level of 23.2 μg/day, which is less than half the safe intake stated by the guidelines, may increase the risk of CKD by 73%, and urinary Cd levels one-tenth of the threshold limit, defined by excessive ß2-microglobulin excretion, were associated with increased risk of CKD, mortality from heart disease, cancer of any site and Alzheimer’s disease. These findings indicate that the current tolerable intake of Cd and the conventional urinary Cd threshold limit do not provide adequate health protection. Any excessive Cd excretion is probably indicative of tubular injury. In light of the evolving realization of the interaction between Cd and Pb, actions to minimize environmental exposure to these toxic metals are imperative.

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Section: Dosimetry and Nephrotoxicity Assessmentmentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

107

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“…The studies measuring individual cadmium levels from blood, urine, or toenails are not necessarily measuring the same timing of exposure. Most [153–155, 159, 162, 163], but not all [158, 164], epidemiologic studies of postmenopausal women or all ages combined show risk estimates in the 0.73 to 1.01 range (Table 2). Two studies show greater risk associated with cadmium exposure for premenopausal women than for postmenopausal women [156, 165], whereas two other studies show the reverse [157, 166], with additional studies describing generally null associations for both groups [160, 161, 167, 168].…”

Section: Introductionmentioning

confidence: 99%

“…difference by ER status ( p = 0.11)0.72–1.41Highest (> 13.3) vs lowest (< 7.48 μg/day) quartile Eriksen (2014) [155]Dietary cadmiumDanish postmenopausal women23,815 total in cohort with 1390 breast cancer casesAll cases IRR 0.99ER+ IRR 1.00ER− IRR 0.880.87–1.130.85–1.150.62–1.22Per 10 μg/day increase in intake Adams (2014) [154]Dietary cadmiumPostmenopausal women aged 50–79 years155,069 total in cohort with 6658 casesHR 0.90n.s. difference by ER status0.81–1.00Highest (> 14.21) vs lowest (< 7.10 μg/day) quintile Adams (2016) [162]Urinary cadmiumPostmenopausal women ages ≥ 50 years in Women’s Health Initiative12,701 total in cohort with 508 cases and 1050 controlsAll HR 0.80ER+ HR 0.98ER−/PR- HR 0.880.56–1.140.87–1.070.70–1.11Highest (> 0.748) vs lowest (< 0.325 μg/g creatinine) quartileAll ages Sawada (2012) [159]Dietary cadmiumJapanese women aged 45–74 years48,351 females total in cohort with 402 breast cancer casesHR 0.870.61–1.23Highest (median 32.3) vs lowest (median 19.2 μg/day) tertile Nagata (2013) [164]Urinary cadmiumJapanese women ages ≥ 25 years153 cases from one hospital and 431 controls invited for breast cancer screeningOR 6.052.90–12.62Highest (> 2.620) vs lowest (< 1.674 μg/g creatinine) tertile Gaudet (2018) [163]Blood cadmiumCancer Prevention Study II women 47–85 years of age816 cases and 816 controlsAll RR 1.01ER+ RR 0.89ER− RR 0.960.76–1.340.62–1.270.44–2.09Continuous per μg/LItalian women aged 35–70 years292 cases and 294 controlsRR 0.800.61–1.03Continuous per μg/LSwedish women aged 30–61 years325 cases and 325 controlsRR 0.730.54–0.97Continuous per μg/LCombined 3 nested case-cohort studies1433 cases and 1435 controlsRR 0.840.69–1.01Continuous per μg/L Abbreviations: BCSC Breast Cancer Surveillance Consortium, CI confidence interval, EPA Environmental Protection Agency, ER estrogen receptor, HR hazard ratio, IRR incidence rate ratio, NHANES National Health and Nutrition Examination Survey, n.s . not statistically significant, OR odds ratio, RR relative risk…”

Section: Introductionmentioning

confidence: 99%

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Michels²,

et al. 2019

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Background The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman’s life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. Main text Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland’s structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals—including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols—and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. Conclusions An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

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“…Recent epidemiological and toxicological studies have reported that lead exposure causes several diseases affecting the cardiovascular system such as hypertension [1] and chronic kidney disease [2,3], as well as the hepatic system [4]. In addition, lead is capable of inducing oxidative stress that damages the brain and affects the life course [5,6], and probably contributes to carcinogenesis [7,8].…”

Section: Introductionmentioning

confidence: 99%

Interactive Effects between Chronic Lead Exposure and the Homeostatic Iron Regulator Transport HFE Polymorphism on the Human Red Blood Cell Mean Corpuscular Volume (MCV)

Chen

Lin

Wang

et al. 2019

IJERPH

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Research has shown that long-term exposure to lead harms the hematological system. The homeostatic iron regulator HFE (hemochromatosis) mutation, which has been shown to affect iron absorption and iron overload, is hypothesized to be related to lead intoxication in vulnerable individuals. The aim of our study was to investigate whether the HFE genotype modifies the blood lead levels that affect the distributions of serum iron and other red blood cell indices. Overall, 121 lead workers and 117 unexposed age-matched subjects were recruited for the study. The collected data included the blood lead levels, complete blood count, serum iron, total iron binding capacity, transferrin, and ferritin, which were measured during regular physical examinations. All subjects filled out questionnaires that included demographic information, medical history, and alcohol and tobacco consumption. HFE genotyping for C282Y and H63D was determined using polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). The mean blood lead level in lead workers was 19.75 µg/dL and was 2.86 µg/dL in unexposed subjects. Of 238 subjects, 221 (92.9%) subjects were wild-type (CCHH) for HFE C282Y and H63D, and 17 (7.1%) subjects were heterozygous for a H63D mutation (CCHD). Multiple linear regression analysis showed that blood lead was significantly negatively associated with hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV), whereas the HFE variant was associated negatively with MCV and positively with ferritin. An interactive influence on MCV was identified between blood lead and HFE variants. Our research found a significant modifying effect of the HFE variant, which possibly affected MCV. The HFE H63D heterozygous (CCHD) variant seemed to provide a protective factor against lead toxicity. Future studies should focus on competing binding proteins between iron and lead influenced by gene variation.

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Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts

Cited by 42 publications

References 44 publications

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Interactive Effects between Chronic Lead Exposure and the Homeostatic Iron Regulator Transport HFE Polymorphism on the Human Red Blood Cell Mean Corpuscular Volume (MCV)

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