Serum immunoglobulin levels and the risk of bladder cancer in the AMORIS Cohort

BackgroundThe anti-tumour T-cell response in bladder cancer has been shown to correlate with response to treatment and prognosis. However, little is known about the role of humoral immunity in this highly immunogenic human cancer, which is characterised by a high mutation-associated neoantigen load and a strong response to immunotherapy. In the present study, we interrogated the Swedish Apolipoprotein Mortality Risk Study (AMORIS) to explore the relationship between pre-diagnostic serum immunoglobulin levels and the risk of developing bladder cancer.MethodsOur analysis included all AMORIS participants aged 20 years or older, who had all three major serum immunoglobulins (IgA, IgM, IgG) recorded at the same baseline measurement (n = 29,876). All participants were free from bladder cancer at the time of measurement. Samples were obtained between 1985–1996, with follow-up information until 2011. Multivariate Cox proportional hazards regression was used to investigate the association between bladder cancer risk and different levels of pre-diagnostic serum immunoglobulins.ResultsDuring a mean follow-up period of 15.31 years, 163 (0.5%) individuals were diagnosed with bladder cancer. Multivariate Cox regression showed an inverse association between pre-diagnostic serum IgM levels ≥ 1.4 g/L and bladder cancer risk compared to serum IgM levels < 1.4 g/L [HR: 0.68 (95% CI 0.45–1.03)]. Corresponding associations could not be established for serum IgA or IgG.ConclusionOur findings implicate serum IgM in the pathogenesis of bladder cancer and suggest that the concept of humoral immune surveillance against cancer warrants further mechanistic investigation.     

Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies

Purpose

Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point.

Methods

We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis.

Results

Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96–1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07–1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72–1.02) or cohort studies (OR = 1.01, 95% CI = 0.91–1.13).

Conclusions

The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association.     

Pre-diagnostic telomere length and colorectal cancer risk

BackgroundProgressive telomere shortening may be related to genomic instability and carcinogenesis. Prospective evidence relating telomere length (TL) with colorectal cancer (CRC) risk has been limited and inconsistent.MethodsWe examined the association between pre-diagnostic peripheral blood leukocyte TL and CRC risk in two matched case-control studies nested within the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Relative leukocyte TL was measured using qPCR among 356 incident CRC cases and 801 controls (NHS: 186/465, HPFS: 170/336).ResultsWe did not find a significant association between pre-diagnostic TL and CRC risk [in all participants, multivariable-adjusted odds ratio (OR) (95% CI) for TL Quartile 1 (shortest) vs. Quartile 4 (longest) = 1.36 (0.85, 2.17), P-trend = 0.27; OR (95% CI) per 1 SD decrease in TL = 1.12 (0.92, 1.36)].ConclusionsOur prospective analysis did not support a significant association between pre-diagnostic leukocyte TL and CRC risk.     

Serum and hair selenium levels in hereditary nonpolyposis colorectal cancer

Since low selenium (Se) levels have been identified in some individuals with colon cancer, we evaluated Se levels as a potential marker for this malignancy in a kindred subject to hereditary nonpolyposis colorectal cancer, an autosomal dominant disease. Unaffected family members and spouses were selected randomly for testing. Serum Se levels were performed on dialyzed sera using the neutron activation technique. Hair Se assays were determined by a spectrofluorometric method. Family members were classified as having low, intermediate, or high risk for colon cancer based on family history. There was no correlation between serum and hair Se measurements. There was also no significant difference in hair or serum Se levels between any of the groups, suggesting that serum Se levels do not correlate with hereditary risk for colon cancer. Prospective studies are in progress to evaluate tissue Se levels and serial Se measurements in high risk patients to establish whether Se levels change with the development of colon cancer.     

Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced thyroid dysfunction compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups receiving either 200 ppm Cd (as CdCl2), 200 ppm Cd + 500 ppm Zn (as ZnCl2), 200 ppm Cd + 0.1 ppm Se (as Na2SeO3), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd exposure increased significantly the relative thyroid weight (RTW), the thyroid Cd concentration, and the serum thyroid stimulating hormone (TSH) level, whereas the serum thyroxine (T4) level was decreased compared to control rats. The treatment of Cd-exposed rats with Se alone only partially protected from the Cd-induced decrease in serum T4 level. The treatment of Cd-exposed animals with Zn alone partially protected against Cd-induced thyroid dysfunction by maintaining normal RTW and by decreasing Cd concentration in the thyroid. It also partially prevents Cd-induced decrease in serum T4 level. The combined treatment of Cd-exposed animals with Se and Zn induced a more significant decrease in the thyroid Cd concentration than the Zn supplement and a total correction of the RTW. This treatment was also more effective than that with Se or Zn alone in reversing Cd-induced decrease in serum T4 level and Cd-induced increase in serum TSH level. Se and Zn can have a synergistic role against Cd-induced thyroid dysfunction.     

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.     

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.     

Uptake of selenium-75 by PHA-stimulated lymphocytes

To determine which of a variety of inorganic and organic selenium compounds could best stimulate glutathione peroxidase, human lymphocytes were cultured with a number of selenium sources. The phytohemagglutinin-transformed lymphocytes were cultured in the presence of⁷⁵Se bound to serum proteins (25% v/v) or 10^?7 M concentrations of [⁷⁵Se]-selenite, [⁷⁵Se]-selenate, [⁷⁵Se]-selenocystine, and [⁷⁵Se]-selenomethionine. Organic forms of selenium were taken up in preference to inorganic forms. Control cultures, from which exogenous selenium had been omitted, showed a decreased level of glutathione peroxidase activity at the end of a 4 d culture period. Of the Se sources tested, [⁷⁵Se]-selenocystine and [⁷⁵Se]-labeled fetal calf serum proteins increased enzyme activity significantly, 79 and 47%, respectively, but selenite increased activity only by 7%. These results indicate that selenium from the two organic sources is most readily available for glutathione peroxidase synthesis.     

Study of distribution and interaction of arsenic and selenium in rat thyroid

Seventy-eight Wistar weanling rats were pretreated with arsenate (100 mg/L As), selenite (1 mg/L Se), and arsenate (100 mg/L As) plus selenite (1 mg/L Se) added to the drinking water. After 4 w, all the animals were sacrificed and serum T3 and T4 were determined by double-antibody radioimmunoassay. Thyroid tissue concentrations of As and Se were determined in female rats by neutron activation analysis, and tissue specimens were examined histopathologically. For both sexes, the measurements indicated that T4/T3 was lowest in the Se group, intermediate in the As group, and highest in the controls. Corrected for the mean value of the controls, mean As concentration of thyroid tissue was of the same magnitude in the group pretreated with As+Se as the sum of the mean As concentration in the groups pretreated with As or Se alone. The outcome was symmetric with regard to the Se concentration: In the As+Se pretreated group, the mean Se concentration was of the same magnitude as the sum of the mean Se concentration in the groups pretreated with As or Se alone. Thus, As and Se tended to accumulate in the thyroid tissue. Postmortem examination showed that the thyroid tissue of rats pretreated with As alone exhibited obvious, toxic changes, whereas only minor or no changes were found in the tissues of the groups pretreated with Se or As+Se, and in the tissues of the controls. Multivariate analyses demonstrated that s-T4 and s-T3 were significantly correlated with sex, that s-T3 was positively correlated (p≤0.001) with Se pretreatment, and that the T4/T3 ratio was negatively correlated with both As (p≤0.012) and Se pretreatment (p≤0.001). The results were discussed in relation to the cancer preventive effect of Se.     

Serine incorporation into the selenocysteine moiety of glutathione peroxidase

The selenium in mammalian glutathione peroxidase is present as a selenocysteine ([Se]Cys) moiety incorporated into the peptide backbone 41-47 residues from the N-terminal end. To study the origin of the skeleton of the [Se]Cys moiety, we perfused isolated rat liver with 14C- or 3H-labeled amino acids for 4 h, purified the GSH peroxidase, derivatized the [Se]Cys in GSH peroxidase to carboxymethylselenocysteine ([Se]Cys(Cm)), and determined the amino acid specific activity. Perfusion with [14C]cystine resulted in [14C]cystine incorporation into GSH peroxidase without labeling [Se]Cys(Cm), indicating that cysteine is not a direct precursor for [Se]Cys. [14C]Serine perfusion labeled serine, glycine (the serine hydroxymethyltransferase product), and [Se]Cys(Cm) in purified GSH peroxidase, whereas [3-3H]serine perfusion only labeled serine and [Se]Cys(Cm), thus demonstrating that the [Se]Cys in GSH peroxidase is derived from serine. The similar specific activities of serine and [Se]Cys(Cm) strongly suggest that the precursor pool of serine used for [Se] Cys synthesis is the same or similar to the serine pool used for acylation of seryl-tRNAs.     

Chemoprevention of prostate cancer with selenium: an update on current clinical trials and preclinical findings

Prostate cancer is the most common cancer diagnosed and the second leading cause of cancer-related deaths in men in the United States. The etiological factors that give rise to prostate cancer are not known. Therefore, it is not possible to develop primary intervention strategies to remove the causative agents from the environment. However, secondary intervention strategies with selenium (Se) compounds and other agents represent a viable option to reduce the morbidity and mortality of prostate cancer. In this review, we discuss ongoing clinical trials. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular basis for the anti-carcinogenic activity of both inorganic and organic forms of Se.     

Risk of thyroid cancer among Chernobyl emergency workers of Russia

The presented paper deals with the thyroid cancer incidence in selected cohorts of emergency workers of Russia. In 1986-2003, a total of 87 cases of thyroid cancer were observed. Based on these data, a statistically significant increase in thyroid cancer incidence was found above the reference level for the male population of Russia, corresponding to a standardized incidence rate (SIR) of SIR = 3.47 [95% confidence interval (CI): 2.80; 4.25]. The highest incidence rate (SIR = 6.62, 95% CI: 4.63; 9.09) was shown for those emergency workers who took part in the early recovery operations in April-July 1986. The estimated SIR value increases to 7.97 (95% CI: 5.24; 11.52) after allowing for a 10 years latent period of Chernobyl-related thyroid cancers. These results indicate that the exposure to incorporated (131)I was the major risk factor of thyroid cancer among Chernobyl emergency workers. No statistically significant relationship was found for the thyroid cancer incidence and external radiation dose.     

Copper,zinc, and selenium in whole blood and thyroid tissue of people with various thyroid diseases

We investigated the possible differences among the concentrations of copper, zinc, and selenium, and their mutual relations in the whole blood and thyroid tissue of patients with various thyroid disorders. Trace elements were determined by total-reflection X-ray fluorescence. The mean levels of these metals in blood as well as the mean Cu/Zn, Cu/Se, and Zn/Se ratios in the patients with thyroid cancer were significantly higher that in other patients and the control groups. However, the mean Zn and Se concentrations in the thyroid cancer tissue were significantly lower than in the thyroid tissue of other patients. In addition, the mean Cu/Zn and Cu/Se ratios in the thyroid cancer tissue were significantly higher than in the patients with other thyroid diseases. We confirm that the highest levels of copper and zinc as well as the Cu/Zn, Cu/Se, and Zn/Se ratios in the whole blood of the patients with thyroid cancer may suggest the progression of the proliferation process in the thyroid gland. We suggest that the low concentrations of zinc and selenium in the thyroid tissue confirm their participation in the carcinogenic process.     

Use of Nonsteroidal Anti-Inflammatory Drugs and Bladder Cancer Risk: A Meta-Analysis of Epidemiologic Studies

Purpose

Several epidemiologic studies have evaluated the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and bladder cancer risk and the results were varied. Thus, we conducted a comprehensive meta-analysis of studies exclusively dedicated to the relationship between the 3 most commonly used analgesics and bladder cancer risk.

Methods

A systematic literature search up to November 2012 was performed in PubMed database for 3 categories of analgesics: acetaminophen, aspirin or non-aspirin NSAIDs. Study-specific risk estimates were pooled using a random-effects model.

Results

Seventeen studies (8 cohort and 9 case-control studies), involving a total of 10,618 bladder cancer cases, were contributed to the analysis. We found that acetaminophen (relative risk [RR] 1.01, 95% confidence interval [CI] 0.88–1.17) and aspirin (RR 1.02, 95% CI 0.91–1.14) were not associated with bladder cancer risk. Although non-aspirin NSAIDs was statistically significantly associated with reduced risk of bladder cancer among case-control studies (but not cohort studies), the overall risk was not statistically significant (RR 0.87, 95% CI 0.73–1.05). Furthermore, we also found that non-aspirin NSAIDs use was significantly associated with a 43% reduction in bladder cancer risk among nonsmokers (RR 0.57, 95% CI 0.43–0.76), but not among current smokers.

Conclusion

The results of our meta-analysis suggest that there is no association between use of acetaminophen, aspirin or non-aspirin NSAIDs and bladder cancer risk. However, non-aspirin NSAIDs use might be associated with a reduction in risk of bladder cancer for nonsmokers.     

Influence of radioactive contamination and iodine prophylaxis after the Czernobyl disaster on thyroid morphology and function of the Poznan region]

The radioactive contamination of Poznań Region was recognized after Chernobyl accident as average. The predicted values of minimal (inhalation) and maximal (inhalation and ingestion) committed dose equivalent to the thyroid varied from 2.5 (min) to 24.7 (max) mSv in different groups of adults and children. To follow up the results of iodine prophylaxis and some aspects of possible thyroid gland morphological and functional changes 11086 persons were carefully investigated clinically and biochemically. Among these 11086 persons were 42.6% males and 57.4% females both adults from 17 till 40 year and children up do 16 years. The following parameters were reviewed: pregnancy, time of residence in the region, thyroid abnormalities, family history concerning thyroid diseases, iodine intake in April and May 1986 with possible side effects, changes in the thyroid size observed before and after 1986, degree and kind of thyroid enlargement, serum concentration of T3, T4, TSH, ATMA and ATG titre and finally the effectiveness of thyroid blockade at 24, 48 and 72 h after ingestion of Lugol's solution. Side effects of the ingestion of potassium iodide from 30-70 mg were observed in 153 cases, 36 of them consulted medical doctors but in no case the side effects (dominated by vomiting) threatened the life. In the investigated group were 144 pregnant women. Majority, because 88% of them delivered the baby on or after time and 6.9% before time, 4.9% of natural abortions were noted but non artificial. In the group of children thyroid gland abnormalities before 1986 were reported in 3 cases in 23 after 1986 it is after Chernobyl accident. This information is interesting but needs more precise analysis of different dependencies occurring. The data obtained indicated the existence in Poznań. Region the goiter endemy because 27.5% of investigated children and adults had goiter classified as grades O-B, I, II and III. The elevation or diminution of T3 values were noted in 1164 cases, for T4 in 418 cases and for TSH in 1412 cases. The presence of antimembrane and antithyroglobulin antibodies were observed in 303 cases. All persons with changes observed in thyroid morphology and function are periodically controlled and the results will be published separately. The investigations performed and results presented concern the early aspects of radioactive contamination and effects of iodine prophylaxis. The answer regarding late effects including thyroid cancer needs further multi year studies for which the clinical material investigated in different parts of Poland and well documented should be used as model group for further periodical studies.     

Energy-Related Indicators and Breast Cancer Risk among White and Black Women

Energy-related indicators, including physical activity, energy intake, body mass index (BMI) and adult weight change, have been linked to breast cancer risk. Very few studies of these associations have been conducted among black women, therefore we used the Nashville Breast Health Study (NBHS) to determine whether similar effects were seen in black and white women. The NBHS is a population-based case-control study of breast cancer among women age 25 to 75 years conducted between 2001 and 2010 in and around the Nashville Metropolitan area. Telephone interviews and self-administered food frequency questionnaires were completed with 2,614 incident breast cancer cases ascertained through hospitals and the statewide cancer registry, and 2,306 controls selected using random digit dialing. Among premenopausal white and black women, there was little effect of adult exercise or other energy-related indicators on breast cancer risk, regardless of tumor estrogen receptor (ER) status. The beneficial effect of adult exercise on postmenopausal breast cancer appeared to be comparable between white and black women (highest tertile relative to none - white odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-1.0, p for trend=0.05; black OR 0.7, 95% CI 0.4-1.1, p for trend=0.07); however, among black women the reduction was limited to those with ER-positive disease. White and black women should be encouraged to engage in more physical activity to reduce their risk of postmenopausal breast cancer.     

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (¹³¹I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the ¹³¹I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.     

Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite

The metabolic detoxification of selenite and many other selenium compounds involves a series of S-adenosylmethionine-dependent methylations yielding dimethylselenide (DMSe), which is exhaled, and trimethylselenonium ion (TMSe), which is excreted in the urine. This paper shows that periodate-oxidized adenosine (Adox) inhibits these methylation reactions in vivo and increases the toxicity of selenite. When Adox was injected in mice at 100 mumol/kg 30 min before injection of [75Se]selenite at 0.4 mg Se/kg the appearances of [75Se]DMSe in the breath and [75Se]TMSe in the liver were completely inhibited for 90 min. This was mediated by accumulation of S-adenosylhomocysteine, the methyltransferase inhibitor, in the livers of Adox-treated mice due to inhibition of its hydrolase enzyme. During 24 h, Adox-treated mice excreted no detectable urinary [75Se]TMSe and exhaled only 20% as much [75Se]DMSe as controls. The urine of Adox-treated mice also contained S-adenosylhomocysteine at a level (ca. 4 mM), 200 times that of untreated mice, which provided a convenient index of methylation potential in the intact animal. When three groups of three mice each were injected with 100 mumol Adox/kg, selenite at 4 mg Se/kg, or a combination of the two, the mice receiving the combination were dead within 2 days, while the mice in the other two groups all survived at least 4 days. These results verify the enzymatic nature of selenium methylation in vivo, support its importance in detoxification, and indicate the value of Adox in further studies of selenium metabolism.     

Serum iron and transferrin during an exhaustive session of interval training

Conflicting data have been reported on "sports anaemia" and anaemia during physical training. Most of these results are of studies at rest before or after training. The aim of this investigation was to further study the profiles of serum iron (Se Fe) and transferrin (Se Tr), in 14 physically trained men (28 +/- 6 years) during an exhaustive interval training session. The 45 min Square-Wave Endurance Exercise Test (SWEET) was performed on a cycle ergometer. To the SWEET base, established as a % of individual VO2max, a peak of 1 min at VO2max was added every 5 minutes. Arterial blood samples were taken at rest, during the SWEET at the 14th, 15th, 29th, 30th, 44th and 45th minutes, just before and after the peaks, and at the 15th min of recovery. Lactate, acidity [H+], PaCO2, PaO2, Haematocrit (Hct), Haemoglobin (Hb), Se Fe and Se Tr were measured. After the SWEET, weight loss was 0.89 +/- 0.15 kg. Lactate and serum iron rose progressively at the base levels and at the peaks, while PaCO2 and bicarbonate fell progressively. Hct, [Hb], serum transferrin and [H+] increased significantly at the 14th min of SWEET and thereafter no change was observed. At the 45th min with respect to the value at rest, Se Fe increased as much as +32%, Se Tr +13% and [Hb] +8%. Haemoconcentration could explain the changes in Se Tr but not the total significant increase in Se, Fe, which moreover is not explained by acidosis [H+].(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactive effects of selenium and chromium on mammary tumor development and growth in MMTV-infected female mice and their relevance to human cancer

Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C₃H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.