Blood selenium concentration in residents of areas in China having a high incidence of lung cancer

Data concerning the blood selenium level and its relation to the mortality from lung cancer are reported. There were 353 samples of blood collected from workers at the Yannan Tin Mine (Yun-Xi) and 75 samples from Beijing residents for comparison. An inverse correlation between blood selenium levels and lung cancer mortalities was observed. The average selenium concentration in whole blood from Beijing residents (age-adjusted mortality rate from lung cancer for males: 12/100,000) and Yun-Xi miners (age-adjusted mortalty from lung cancer for males: 108/100,000) were 12.3 and 8.8 μg/100 mL, respectively. A similar inverse correlation was also observed among young people of comparable sex and age groups. In Yun-Xi, the tin miners working underground with an average lung cancer death rate of 250/100, 000 for males had lower blood selenium concentrations than those working above ground, where the average lung cancer death rate for males was 42/100,000. Workers frequently exposed to arsenic exhibited lower blood selenium contents. Selenium levels in the blood of patients with lung cancer were lower (6.2 μg/100 mL) than those of healthy controls.     

Selenium chemoprevention of liver cancer in animals and possible human applications

An inverse correlation between geographic distribution of liver cancer incidence and the selenium (Se) contents of whole blood and grains was observed in Qidong county, Jiangsu province, a high liver cancer area of the People’s Republic of China. Animal experiments demonstrated that supplementation of Se reduced the incidence of liver cancer in rats exposed to aflatoxin B₁. Se was also shown to inhibit the growth of transplanted tumors. A lower incidence of liver preneoplastic alterations and reduction of hepatitis B virus infection in ducks by Se-supplementation was observed, and three pilot studies for a Se-intervention trial on human liver cancer were carried out on the residents of Qidong county. A protective effect on the cellular DNA damage induced by aflatoxin B₁ was observed in lympocytes from human with Se-supplements.     

Regional trends in prostate cancer incidence,treatment with curative intent and mortality in Norway 1980–2007

Objectives: To compare the trends in prostate cancer incidence, treatment with curative intent and mortality across regions and counties in Norway, and to consider changes in incidence (an indicator for early diagnosis) and treatment with curative intent as explanatory factors for the decreasing prostate cancer mortality rates. Patients and methods: Prostate cancer incidence and mortality data (1980–2007) alongside treatment data (1987–2005) were obtained from the national, population-based Cancer Registry of Norway. Joinpoint regression models were fitted to age-adjusted incidence, treatment and mortality rates to identify linear changes in the trends. Results: Both age-adjusted incidence rates and rates of curative treatment of prostate cancer increased significantly in all five regions of Norway since the early 1990s. There was a strong positive correlation between increasing incidence and increasing use of curative treatment. The frequency of curative treatment in Western Norway was almost threefold that in the Northern and Central regions around year 2000. Subsequently, the regional trends converged and only minor differences in prostate cancer incidence and use of curative treatment were observed by 2005. The declines in mortality were observed earliest in the regions with the highest incidence and the most frequent use of curative treatment, while the largest decreases in mortality were found in counties where the largest increases in curative treatment were observed. Conclusions: The elucidation of the prostate cancer mortality trends is hindered by an inability to tease out the potential effects of early treatment from the more general impact of improved and more active treatment. However, it is likely that both sets of intervention have contributed to the decline in prostate cancer mortality in Norway since 1996.     

Selenium status of Omsk oblast

For 32 districts of Omsk oblast, the levels of selenium accumulation were determined across trophic levels: soil, plants, animals, and human. An inverse correlation was found between serum selenium concentration and parameters of total mortality, as well as the incidence of lung, ovarian, and rectal cancer. Significant differences were shown in the coefficient of plant selenium accumulation depending on the soil type. We discuss the most promising approaches to optimizing the selenium status of the population.     

Associations of total blood mercury and blood methylmercury concentrations with diabetes in adults: An exposure-response analysis of 2005-2018 NHANES

ObjectiveTo examine the exposure-response relationship between mercury exposure and diabetes in adults, and to explore the possible effect modifications by selenium and omega-3 fatty acids.MethodsBiomarker data (total blood mercury and blood methylmercury) from individuals ≥20 years of age were obtained from the 2005–2018 NHANES. Diabetes was defined through questionnaires, fasting plasma glucose, 2 -h plasma glucose and hemoglobin A_1c levels. The exposure-response relationship between mercury exposure and diabetes was assessed with logistic regression and restricted cubic splines.ResultsComparing the highest to lowest quartile of exposure, the multivariable-adjusted odds ratio (95 % CI) of diabetes was 0.76 (0.63−0.92) with total blood mercury and 0.82 (0.66−1.00) with blood methylmercury. The inverse associations between total blood mercury [0.55 (0.40−0.77)] and blood methylmercury [0.61 (0.38−0.97)] and diabetes were observed among individuals having higher intakes of selenium (P_{for interaction}<0.05). Trends toward lower odds of diabetes with mercury exposure were mainly confined to individuals having higher intakes of omega-3 fatty acid, but the interactions were not significant. The inverse associations between total blood mercury and blood methylmercury and diabetes remained in sensitivity analyses after excluding patients with hypertension that may change their dietary intake of fish. Exposure-response analyses showed an initial decrease in odds of diabetes followed by a platform or a weaker decrease beyond 3 μg/L of total blood mercury and methylmercury concentrations, respectively.ConclusionsTotal blood mercury and blood methylmercury concentrations were inversely associated with diabetes in adults, and the associations were modified by selenium.     

The distribution of selenium and cancer mortality in the continental United States

An hypothesis was proposed that selenium concentration in the environment, as measured by the uptake of this element by forage crops, exerted an apparent effect on cancer incidence, such that cancer mortality in the continental United States was lower where the selenium concentration was high than where the concentration was low. The purpose of the present study is to test this hypothesis for statistical significance and to discover whether the apparent pattern of cancer mortality in relation to selenium distribution holds true with respect to all ages. Two main types of statistical analyses were employed: analysis of variance and trend analysis, both applied to all age groups and both sexes. Data presented in this paper show that significant interactions exist between selenium distribution and sex in relation to deaths caused by cancer of the digestive organs, respiratory organs, and the breast. Geographic variations in selenium may be viewed as variations in the intake of this element in the diet. A significant interaction may thus suggest that the particular cancer in question has in its origin a dietary factor that includes some measure of selenium intake. A discussion involving contributions from various disciplines is presented to explain the significant results reported in this paper. This paper shows that a pattern exists between the geographical distribution of selenium using forage crops as a guide for dietary intake and cancer mortality (ICD 140-209,150-159,160-163, and 174) such that an inverse relationship exists between selenium concentration in an area and cancer mortality in the same area.     

Educational inequalities in cancer incidence and mortality in Lithuania: A record linkage study

BackgroundThe aim of this study is to describe associations between incidence and mortality by major cancer sites and education in Lithuania.MethodsThe study is based on the linkage between all records of the 2001 population census and all records from Lithuanian Cancer Registry (cancer incidence) and Statistics Lithuania (deaths) for the period between 1 July 2001 and 31 December 2004. Education-specific incidence and mortality rate ratios were estimated by means of multivariate Poisson regression models.ResultsWe found both the positive and inverse educational gradients in cancer incidence and mortality. The risk of developing cancer (all sites) was lower among men and women with the lowest education, whereas cancer mortality was higher among lower educated men. The higher educational level was also associated with an increased risk of prostate cancer among men and an increased risk of breast cancer among women. However, prostate cancer mortality was the highest in the lowest education group, whereas breast cancer mortality among women did not show any statistically significant differences. Lower educated men had significantly higher incidence and mortality due to lung and stomach cancers. Strikingly high incidence and mortality due to cervix cancer was observed among women with secondary and lower than secondary education.ConclusionThe results point to inequalities in early diagnosis and survival from cancer and failures ensuring equal access to medical care. Further more in-depth studies are needed in order to understand the nature and determinants of these inequalities.     

Focus: A Multifaceted Battle Against Cancer: Gene-by-Environment Interactions in Pancreatic Cancer: Implications for Prevention

Pancreatic cancer (PC) has been estimated to have higher incidence and correspondingly higher mortality rates in more developed regions worldwide. Overall, the age-adjusted incidence rate is 4.9/10⁵ and age-adjusted mortality rate is at 4.8/10⁵. We review here our current knowledge of modifiable risk factors (cigarette smoking, obesity, diet, and alcohol) for PC, genetic variants implicated by genome-wide association studies, possible genetic interactions with risk factors, and prevention strategies to provide future research directions that may further our understanding of this complex disease. Cigarette smoking is consistently associated with a two-fold increased PC risk. PC associations with dietary intake have been largely inconsistent, with the potential exception of certain unsaturated fatty acids decreasing risk and well-done red meat or meat mutagens increasing risk. There is strong evidence to support that obesity (and related measures) increase risk of PC. Only the heaviest alcohol drinkers seem to be at an increased risk of PC. Currently, key prevention strategies include avoiding tobacco and excessive alcohol consumption and adopting a healthy lifestyle. Screening technologies and PC chemoprevention are likely to become more sophisticated, but may only apply to those at high risk. Risk stratification may be improved by taking into account gene environment interactions. Research on these modifiable risk factors is key to reducing the incidence of PC and understanding who in the population can be considered high risk.     

Geographic variations in cancer incidence and mortality in the State of São Paulo,Brazil 2001–17

BackgroundCancer is a leading cause of morbidity and mortality in Brazil and the burden is rising. To better inform tailored cancer actions, we compare incidence and mortality profiles according to small areas in the capital and northeast region of the State of São Paulo for the leading cancer types.MethodsNew cancer cases were obtained from cancer registries covering the department of Barretos (2003–2017) and the municipality of São Paulo (2001–2015). Cancer deaths for the same period were obtained from a Brazilian public government database. Age-standardized rates per 100,000 persons-years by cancer and sex are presented as thematic maps, by municipality for Barretos region, and by district for São Paulo.ResultsProstate and breast cancer were the leading forms of cancer incidence in Barretos, with lung cancer leading in terms of cancer mortality in both regions. The highest incidence and mortality rates were seen in municipalities from the northeast of Barretos region in both sexes, while elevated incidence rates were mainly found in São Paulo districts with high and very high socioeconomic status (SES), with mortality rates more dispersed. Breast cancer incidence rates in São Paulo were 30 % higher than Barretos, notably in high and very high SES districts, while corresponding rates of cervical cancer conveyed the opposite profile, with elevated rates in low and medium SES districts.ConclusionsThere is substantial diversity in the cancer profiles in the two regions, by cancer type and sex, with a clear relation between the cancer incidence and mortality patterns observed at the district level and corresponding SES in the capital.     

Acute human toxicity and mortality after selenium ingestion: A review

BackgroundAlthough selenium is an essential element for humans, acute toxicity has been reported after high oral exposure.MethodsThe published literature on the acute toxicity of oral selenium was gathered and reviewed.ResultsReported symptoms and signs include abdominal symptoms, such as vomiting, diarrhea, pain, and nausea, as well as garlic-like odor on the breath. In cases of severe toxicity, cardiac and pulmonary symptoms may develop and ultimately lead to mortality. Mortality has been described after the ingestion of gun bluing solutions, which often contain selenous acid among other potentially toxic substances. Mortality has also been reported after the ingestion of other forms of selenium. Ingested doses associated with mortality are in the range of 1–100 mg Se/kg body weight. Blood levels associated with mortality are above 300 μg Se/L (normal level: 100 μg/L), whereas urinary levels associated with the same endpoint are above170 μg Se/L (normal level: 20–90 μg/L).ConclusionThe acute toxicity associated with oral selenium ingestion and the blood and urinary levels of selenium in different cases of poisonings were reviewed. Mortality is a risk of acute selenium poisoning. Concentrations of selenium in blood and urine samples in non-fatal cases are close to those observed in fatal cases.     

Anti-oxidant supplementation decreases TBA reactants in serum of elderly

An “anti-oxidant cocktail” consisting of betacarotene, vitamins B₆, C, E, zinc, and selenium or corresponding placebos were given for one y as daily dietary supplements to 45 elderly residents of a nursing home. Initially, the serum TBA reactant levels were higher (2.7±0.7 μmol/L) than those of an ad hoc control group of healthy younger adults (2.3±0.6 μmol/L),p<0.01. After three mo supplementation, the levels among the verum elderly had decreased to 2.2±0.6 μmol/L, and they remained at this lower level until the end of the study period, whereas the placebo group showed no change. A significant inverse correlation (r=−0.428,p<0.01) existed between the concentrations of serum TBA reactants and whole blood selenium (B-Se), but only B-Se levels above 200 μg/L were associated with a decrease in serum lipid peroxides. Serum alpha-tocopherol concentration also correlated inversely with serum TBA reactants but this correlation (r=−0.273,p<0.76) was not as strong as that of B-Se. Deficient vitamin B₆ status, in biochemical terms, was observed in 25% of the elderly; a daily supplement of 2 mg B₆ fully cured all cases of deficiency. The verum group improved slightly in several psychological tests, whereas subjects on placebo remained unchanged or deteriorated during the follow-up period. Clinical amelioration among the verum subjects was reported by the nurses; no toxic side effects were reported. In conclusion, the elderly benefited biochemically and clinically of dietary antioxidant supplements.     

Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial

Background/Objectives

Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q₁₀, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality.

Subjects/Methods

437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots.

Results

The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group.

Conclusion

CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q₁₀ combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area.     

Comparative Excretion and Tissue Distribution of Selenium in Mice and Rats Following Treatment with Diphenyl Diselenide

The purpose of this study was to provide data about in vivo tissue distribution and excretion of diphenyl diselenide ((PhSe)₂) in rats and mice through determination of selenium levels in different biological samples. (PhSe)₂ (500?mg/kg, dissolved in canola oil) was administered to animals once a day per oral. After this, mice and rats were housed in metabolic cages (one animal per cage) and urine and feces were collected at specific times after treatment. Three to five animals per group (for each time-point) were anesthetized and blood samples were collected at 0 and 30?min, 24?h, at day 5, 15, and 30 after (PhSe)₂ administration. The plasma and red blood cells were separated. Brain, liver, lungs, kidneys, and adipose tissue were also collected. The determination of selenium levels was performed by inductively coupled plasma atomic emission spectrometry. The main results indicate that: (1) urine is an important route of excretion of selenium originated from (PhSe)₂ in mice and rats; (2) a large amount of (PhSe)₂ or some of its metabolites are stored in fat; (3) the content of selenium found in plasma was low; and (4) liver and kidneys are the tissues with high amounts of selenium.     

An age-stratified poisson model for comparing trends in cancer rates across overlapping regions

The annual percent change (APC) has been used as a measure to describe the trend in the age-adjusted cancer incidence or mortality rate over relatively short time intervals. The yearly data on these age-adjusted rates are available from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The traditional methods to estimate the APC is to fit a linear regression of logarithm of age-adjusted rates on time using the least squares method or the weighted least squares method, and use the estimate of the slope parameter to define the APC as the percent change in the rates between two consecutive years. For comparing the APC for two regions, one uses a t-test which assumes that the two datasets on the logarithm of the age-adjusted rates are independent and normally distributed with a common variance. Two modifications of this test, when there is an overlap between the two regions or between the time intervals for the two datasets have been recently developed. The first modification relaxes the assumption of the independence of the two datasets but still assumes the common variance. The second modification relaxes the assumption of the common variance also, but assumes that the variances of the age-adjusted rates are obtained using Poisson distributions for the mortality or incidence counts. In this paper, a unified approach to the problem of estimating the APC is undertaken by modeling the counts to follow an age-stratified Poisson regression model, and by deriving a corrected Z -test for testing the equality of two APCs. A simulation study is carried out to assess the performance of the test and an application of the test to compare the trends, for a selected number of cancer sites, for two overlapping regions and with varied degree of overlapping time intervals is presented.     

The Epidemiology of Thyroid Cancer in Los Angeles County

More than 300 new cases of thyroid cancer are diagnosed in Los Angeles County every year. The age-adjusted annual incidence rates of this disease for all races combined are 2.4 for males and 6.1 for females. Rates for women are more than twice rates for men in each major ethnic group. Blacks of both sexes have the lowest rates; Japanese, Chinese, other Asians and Spanish-surnamed whites all have rates that are as high as or higher than rates among non-Spanish-surnamed whites. Other demographic patterns include the excess of thyroid cancer among Jewish residents of Los Angeles.There have been an increase in thyroid cancer incidence and a decline in mortality for this disease in the United States over the past several decades. Several possible explanations can be made for these trends. Also, the risk factors for thyroid cancer deserve review.     

Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice,while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα

Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (Trsp^tG37) and/or a cancer driver TGFα transgene. The use of Trsp^tG37 altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. Trsp^tG37 transgenic and TGFα/Trsp^tG37 bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα–induced liver tumors.     

Neighborhood Deprivation and Risk of Cancer Incidence,Mortality and Survival: Results from a Population-Based Cohort Study in Japan

Background

In many developed countries, socioeconomic status is associated with cancer incidence and survival. However, research in Japan is sparse. We examined the association between neighborhood deprivation based on the Japanese Deprivation Index and the risk of incidence, mortality and survival from total and major cancers in the Japan Public Health Center-based Prospective Study.

Methods

86,112 participants were followed through the end of 2009. A total of 10,416 incident cases and 5,510 deaths from cancer were identified among 1,348,437 person-years of follow-up (mean follow-up: 15.7 years). The Japanese deprivation index was used to access neighborhood deprivation. Hazard ratios and 95% confidence intervals were calculated by Cox regression analysis.

Results

We found no associations between neighborhood deprivation index and the incidence of total and major cancers. In some cancer risks or deaths, however, we found positive or inverse associations with a higher deprivation index, such as a decreased risk of colorectal cancer incidence and an increased risk of liver cancer incidence and deaths in women.

Conclusion

Although some positive or inverse associations were detected for specific sites, the neighborhood deprivation index has no substantial overall association with the risk of incidence, mortality and survival from cancer in the Japanese population.     

Cancer Incidence following Expansion of HIV Treatment in Botswana

BackgroundThe expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa.MethodsWe included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003–2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage.FindingsDuring this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi’s sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%).InterpretationExpansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa.