Cadmium levels in human breast tissue and estradiol serum levels: Is there a connection? (original) (raw)

Association between cadmium and breast cancer risk according to estrogen receptor and human epidermal growth factor receptor 2: epidemiological evidence

Breast Cancer Research and Treatment, 2014

The study aimed to examine the association between cadmium (Cd) and the risk of breast cancer according to estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). A hospital-based casecontrol study was carried out in 585 cases and 1,170 controls. Information on possible risk factors was collected via a structured questionnaire. Urinary Cd was determined by atomic absorption spectrometry. The ER and HER2 levels in tumor tissue were analyzed by immunohistochemistry. Logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for breast cancer by creatinine-adjusted urinary Cd. Women with greater creatinine-adjusted urine Cd (3rd quartile: 0.241-0.399 lg/g and 4th quartile: C0.4 lg/g) experienced 1.6 times higher risk of breast cancer compared with those having Cd concentration lower than 0.147 lg/g (1st quartile) [

In-Vivo and In-Vitro Study of the Relation Between Cadmium and Breast Cancer by

Cadmium is a potent carcinogenic environmental pollutant that has been lastly linked to breast cancer. This research was done to find out the role of cadmium in induction of breast cancer both in-vivo and in-vitro. In-vivo study was conducted on 100 female patients who were randomly chosen from those attending Oncology Center, Mansoura University. Cadmium concentration was measured in urinary and tissue samples from 75 patients with breast cancer (test group) and 25 patients with benign breast diseases (positive control group), using inductive coupled plasma (ICP)-spectrometer. In-vitro study included primary cultured normal mammary cells that were divided into test group (treated with CdCl 2 at a concentration of 15µM) and a matched control group (untreated cultured mammary cells). Cell viability and bleomycin dependent DNA damage were evaluated. In-vivo study shows significant increases in urinary and tissue cadmium concentrations in breast cancer patients compared to their corresponding controls (p=0.000). Regarding in-vitro study, significant reduction in cell viability associated with significant increase in DNA damage were observed (p<0.05). It could be concluded that the present study posits a causal association between cadmium exposure and breast cancer.

Cadmium Exposure and Risk of Breast Cancer by Histological and Tumor Receptor Subtype in White Caucasian Women: A Hospital-Based Case-Control Study

International Journal of Molecular Sciences, 2019

As the majority of experimental studies suggest cadmium being metalloestrogen, we examined cadmium/breast cancer (BC) association by histological and tumor receptor subtype in 509 invasive BC patients and 1170 controls. Urinary cadmium was determined by atomic absorption spectrometry, and categorized using tertiles of its distribution in the controls: <0.18, 0.18–0.33, >0.33 kg × 10−9/kg × 10−3 creatinine. Relative to the lowest category of urinary cadmium adjusted odds ratio (OR) of ductal BC was 1.18 (95% confidence interval (CI): 0.89–1.58) in the intermediate and 1.53 (95% CI: 1.15–2.04) in the highest category. There was a significant association for hormone receptor-positive ductal BC: ORs per category increase were 1.34 (95% CI: 1.14–1.59) for estrogen receptor-positive (ER+), 1.33 (95% CI: 1.09–1.61) for progesterone receptor-positive (PR+) and 1.35 (95% CI: 1.11–1.65) for ER+/PR+ BC. We found a significant association between cadmium and human epidermal growth factor ...

Cadmium Exposure and Breast Cancer Risk

JNCI Journal of the National Cancer Institute, 2006

Cadmium, a highly persistent heavy metal, has been categorized as a probable human carcinogen by the U.S. Environmental Protection Agency. Primary exposure sources include food and tobacco smoke. We carried out a population-based case -control study of 246 women, aged 20 -69 years, with breast cancer and 254 agematched con trol subjects. We measured cadmium levels in urine samples by inductively coupled plasma mass spectrometry and conducted interviews by telephone to obtain information on known breast cancer risk factors. Odds ratios (ORs) and 95% confi dence intervals (CIs) for breast cancer by creatinine-adjusted cadmium levels were calculated by multivariable analysis. Statistical tests were two-sided. Women in the highest quartile of creatinine-adjusted cadmium level ( ≥ 0.58 µg/g) had twice the breast cancer risk of those in the lowest quartile (<0.26 µg/g; OR = 2.29, 95% CI = 1.3 to 4.2) after adjustment for established risk factors, and there was a statistically signifi cant increase in risk with increasing cadmium level ( P trend = .01). Based on this study, the absolute risk difference is 45 (95% CI = 0 to 77) per 100 000 given an overall breast cancer rate of 124 per 100 000. Whether increased cadmium is a causal factor for breast cancer or refl ects the effects of treatment or disease remains to be determined. [J Natl Cancer Inst 2006;98: 869 -73 ]

Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells

Journal of Biological Chemistry, 1994

The effects of cadmium on estrogen receptor and other estrogen-regulated genes in the human breast cancer cell line MCF-7 were studied. Treatment of MCF-7 cells with 1 p~ cadmium decreased the level of estrogen receptor 58%. Cadmium induced a parallel decrease in estrogen receptor mRNA (62%). Progesterone receptor levels increased 3.2-fold after cadmium treatment. This induction was blocked by the anti-estrogen ICI-164,384. Progesterone receptor mRNA was also increased by cadmium, as well as cathepsin D mRNA. An in vitro nuclear transcription run-on assay showed that cadmium increased the transcription of the progesterone receptor and pS2 genes and decreased transcription of the estrogen receptor gene. These are not general effects of heavy metals, as zinc, 25 and 100 p~, did not affect progesterone receptor protein and mRNA levels. Cadmium stimulated pS2 and progesterone receptor mRNAs in a clone of MDA-MB-231 cells transfected with the human estrogen receptor, but had no effect in

Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland

Nature Medicine, 2003

It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor 1,2 . The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.

Cadmium concentration in biological media of breast cancer patients

Breast Cancer Research and Treatment, 2010

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Dietary Cadmium Exposure and Risk of Breast, Endometrial, and Ovarian Cancer in the Women’s Health Initiative

Environmental Health Perspectives, 2014

Purpose: Cadmium is a human lung carcinogen and possesses estrogen-like activity. This combination of carcinogenic and estrogenic activity makes cadmium a contaminant of high concern for hormone-related cancers. Diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal woman. Methods: We estimated dietary cadmium intake in the Diet, Cancer and Health cohort at enrolment 1993-97. The estimates were based on food frequency questionnaires and cadmium contents in all foods. Among 23,815 postmenopausal women we identified 1390 breast, 192 endometrial, and 146 ovarian cancer cases from enrolment through December 31, 2010 using the Danish Cancer Registry. Cox regression was used to analyse the association between dietary cadmium intake and cancer risk. Results: Mean dietary cadmium intake was 14 mg/day. Cadmium was not associated with breast cancer, incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI): 0.87-1.13 per 10 mg higher dietary cadmium intake/day; endometrial cancer, IRR = 1.08, 95% CI: 0.76-1.53; or ovarian cancer, IRR = 1.15, 95% CI: 0.78-1.70. We found a positive association between cadmium and endometrial cancer for the women with BMI,25 (IRR = 1.50, 95% CI: 0.94-2.39), whereas an inverse association was seen for the women with BMI$25 (IRR = 0.69, 95% CI: 0.42-1.12); p value for interaction = 0.02. Conclusions: Our study does not indicate that our estimated dietary cadmium intake is associated with hormone-related cancers in women.

Urinary cadmium and mammographic density in premenopausal women

Breast Cancer Research and Treatment, 2011

Purpose-Mammographic density (MD), a strong marker of breast cancer risk, is influenced by genetic, environmental, and hormonal factors. Cadmium, a persistent and widespread environmental pollutant, has been associated with risk of breast cancer, and laboratory evidence suggests cadmium is a carcinogen in the breast. We investigated the hypothesis that cadmium exposure is associated with higher MD. Methods-In a cross-sectional study of MD and urinary cadmium concentration, percentage MD (MD%) and Breast Imaging-Reporting and Data Systems (BI-RADS ®) density category were determined from screening mammograms of 190 premenopausal women ages 40-45 years. Women completed a health questionnaire, and the cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and corrected for urine creatinine. Urinary cadmium concentrations are thought to reflect exposure to cadmium over a period of 20-30 years. Multivariable linear regression and logistic regression were used to estimate the strength of association between urinary cadmium and mammographic breast density. Results-Adjusted mean MD% among women in the upper tertile of creatinine-corrected urine cadmium was 4.6% higher (95% confidence interval (CI): −2.3 to 11.6%) than in women in the lowest cadmium tertile. Each twofold increase in urine cadmium was associated with higher odds of MD% in the upper tertile (odds ratio(OR): 1.29, 95% CI: 0.82-2.02) or a BI-RADS category rating of "extremely dense" (OR: 1.75, 95% CI: 1.14-2.70). Stronger associations were observed among nulliparous women, and current or former smokers. Conclusions-Exposure to cadmium may be associated with increased breast density in premenopausal women.