Breast Cancer Recurrence and Selenoprotein P Autoimmunity

Breast cancer prognosis is especially poor in patients with low serum selenium and serum selenoprotein P concentrations. Now, researchers have discovered natural autoantibodies with antagonistic properties to selenoprotein P uptake in breast cancer patients and  in patients with thyroid disease [Demircan 2022; Sun 2022].

Autoimmunity
Autoimmunity is the production of antibodies against the tissues or substances of one’s own body, resulting in an autoimmune disease or hypersensitivity reaction. Autoantibodies to Selenoprotein P impair the transport of the essential trace element selenium in breast cancer patients and in Hashimoto’s thyroiditis patients.

Selenium is an essential trace element that has numerous biological functions in the body, most of which are carried out by selenium-containing selenoproteins. Among the more important selenoproteins are selenoprotein P, the main transporter of selenium in the blood, and glutathione peroxidase 3 (GPX3), an important antioxidant.

The human body does not synthesize selenium. Human cells are dependent upon selenium sources in the diet. Unfortunately, the selenium content in the soil and in food varies considerably from region to region in the world. For example, the plasma selenium concentrations in people living in much of Europe are generally below, often well below, 80–90 mcg/L whereas people living in North America generally have plasma selenium levels above 120 mcg/L [Alehagen 2022]. read more

Selenium Exposure Studies

Selenium exposure in the diet and in supplements: in this review article, we summarize the key outcomes of the best selenium exposure studies.

Optimal Selenium Intake and Status

In his review of the available research literature, Professor Urban Alehagen, Linköping University, Sweden, concluded that a daily intake of 100–150 mcg of selenium per day is required.

This is the intake level that enables an optimal expression of the important selenoprotein P that transports selenium from the liver to peripheral tissues [Alehagen 2022].  For other selenoproteins to be optimized, i.e., to be fully expressed, Prof. Alehagen argues that selenium status of approximately 120 mcg/L when measured in red blood cells is necessary [Alehagen 2022]. read more

Serum Selenium Levels Predict Breast Cancer Prognosis

Research done in southern Sweden shows that three blood biomarkers of selenium availability correlated inversely with mortality from breast cancer. The lower the three selenium biomarker levels, the higher the mortality [Demircan 2021].

Breast cancer awareness
Assessment of selenium status at the time of breast cancer diagnosis identifies patients at exceptionally high risk for a poor prognosis. They are breast cancer patients with low levels of selenium, selenoprotein P, and glutathione peroxidase in their blood.

The blood biomarkers are:

  • Total selenium
  • Selenoprotein P
  • Glutathione peroxidase 3

Breast cancer patients with blood concentrations of these three selenium biomarkers in the highest quintile had significantly better chances of survival compared with patients whose blood levels of these substances were in the lowest quintile [Demircan 2021].

Breast cancer patients with low selenium status according to these three biomarkers had the highest mortality risk with an overall survival probability of approximately 50% after 8 years. The difference in survival between the breast cancer patients in the lowest selenium quintile compared to breast cancer patients with at least one biomarker in the highest quintile was especially notable [Demircan 2021]. read more

Serum Selenium Status and Cancer Risk

On its Selenium: Fact Sheet for Health Professionals website, the US Office of Dietary Supplements, an agency of the National Institutes of Health, writes that selenium might play a role in the prevention of cancer for the following reasons:

  • selenium’s role in DNA repair
  • selenium’s role in apoptosis
  • selenium’s role in the endocrine and immune systems
  • the antioxidant properties of certain selenoproteins
Cancer prevention ribbons
It is not possible to draw any conclusions regarding a causal link between selenium exposure/status and the prevention of cancer. However, numerous observational studies show an inverse relationship between serum selenium status and the risk of cancer.
Different Selenium Compounds Have Different Effects on Cancer

The evidence from scientific research into the effect of selenium on cancer prevention can be confusing. Two observations about selenium supplementation may help to explain the confusing results from existing selenium and cancer studies:

1. Different selenium containing compounds differ widely in their ability to prevent cancer. Study results may vary according to the form of the selenium supplement tested.

2. Selenium supplementation may be more effective at cancer prevention in study participants with low baseline selenium status (below 100 mcg/L) and less effective in study participants with high baseline selenium status (above 135 mcg/L). read more

Selenium Supplementation and Prostate Cancer

New Zeland landscape
The New Zealand study results suggest that each of us needs to take personalized selenium supplement dosages based on our individual characteristics rather than have all of us take the same 200 microg/day tablet for prostate health benefits [Karunasinghe 2019].
Demographic, dietary, genetic, and life style factors influence the prostate health effects of selenium supplementation according to New Zealand researchers.

An inverse association between serum selenium concentrations and prostate-specific antigen levels was especially strong in the following sub-groups of study participants [Karunasinghe 2019]:

  • men below the age of 55 years
  • men who never smoked
  • men carrying the GPX1 rs1050450 T allele
  • men with dietary intakes above the recommended daily intake for zinc (11 mg)
  • men with dietary intakes below the recommended daily intake for vitamin B12 (15 mcg)

Moreover, the increase in serum selenium status and the resulting post-supplementation serum selenium status were significantly dependent upon baseline serum status [Karunasinghe 2019].

The overall gain in serum selenium levels from supplementation declined at a rate of 0.828 microg/L with each one microg/L increase in baseline serum selenium level [Karunasinghe 2019]. read more

Selenium Intakes and the Risk of Cancer: Two Meta-Analyses

Blue ribbon for prostate cancer
Despite the billions of dollars spent in the war on cancer, cancer in its various forms continues to be a leading cause of death worldwide. Treatment is expensive. The prognosis is often poor. Even so, the World Health Organization estimates that perhaps one third of all cancer cases could be prevented with changes in behavioral and dietary patterns. An inverse linear association has been found between increased selenium intake and reduced risk of all cancers. As the selenium intake increased, the overall risk of cancer incidence decreased [Kuria 2020].
A 2020 meta-analysis of population-based prospective studies shows that selenium supplementation is protective against cancer; however, the beneficial effects of the selenium supplementation vary with the different types of cancer. The differences in the effect of selenium intakes on the risk of various cancer forms has been attributed to differences in the pathophysiology of cancer [Kuria 2020].

Briefly, the data from the meta-analysis show that selenium decreases the risk of cancer at the highest daily intake levels of the included studies.

This outcome is consistent with the outcomes of a previous study showing a protective effect of selenium at high doses compared to low doses [Cai 2016]. A 2018 meta-analysis used different methods to assess selenium exposure and showed a null association between selenium at high doses compared to low doses [Vinceti 2018]. read more

Selenium Status and Prostate Cancer Risk

The light blue ribbon is the prostate cancer awareness ribbon. Along with skin cancer, prostate cancer is the most common cancer among American men. The American Cancer Society estimates that one man in nine will be diagnosed with prostate cancer during his lifetime. Research shows that blood selenium status within a specific range is associated with reduced risk of prostate cancer.

One of the big challenges in selenium research is the optimizing of the daily selenium intake to reduce the risk of prostate cancer. We need more research results to answer the following questions about the use of selenium supplements to reduce the risk of prostate cancer [Waters & Chiang 2017]:

  • What is the optimal formulation of the selenium supplement?
  • What is the correct daily dosage?
  • What is the range of baseline blood selenium concentrations that indicates a need for selenium supplementation?
  • What is the blood selenium level above which selenium supplementation will not reduce the risk of prostate cancer further?

The idea that selenium intakes and selenium status are an important determinant of prostate cancer risk began to receive considerable attention after University of Arizona Professor Larry Clark published the results of the Nutritional Prevention of Cancer Trial in JAMA in December 1996 [Clark 1996].

High-Selenium Yeast Supplements in the Nutritional Prevention of Cancer Trial

The Nutritional Prevention of Cancer Trial (NPCT) was a supplementation trial using 200 micrograms of a selenized yeast preparation or placebo for an average duration of 4.5 years.  The study participants were 1312 men and women with an average age 63 years. read more

Selenium For Cancer Treatment

Pre-clinical studies suggest that selenium supplementation in the right formulation and the right dosage may enhance the effects of chemotherapy for certain forms of cancer. Selenium may help to protect normal cells and tissues against the toxicities of chemotherapy drugs.  Selenium may enable the administration of higher than normal doses of the chemotherapy drugs.

Chemotherapy and radiation continue to be the major forms of treatment for many types of cancer. The considerable toxicity of these treatments to normal cells is a problem in cancer treatment and management.

Selenium’s Role in Cancer Prevention

Selenium supplementation has already been associated with statistically significant reductions in the risk of various cancers and pre-cancerous conditions:

Possible Role for Selenium in Cancer Treatment

Selenium supplementation may be valuable in the treatment of cancer as well as in the prevention of cancer.  Selenium has the ability to protect against the formation and progression of some cancer cells and also the ability to selectively target some existing cancer cells.

Moreover, it may be that selenium can work in synergy with conventional cancer therapies.  Pre-clinical research data suggest that selenium may in some instances protect normal cells and tissues against the toxic effects of conventional cancer treatments on the cells [Evans 2017]. read more

Blood selenium concentrations and high-grade prostate cancer

A 2012 meta-analysis and systematic review has shown an inverse association between plasma/serum selenium levels and prostate cancer advanced prostate cancer in particular. Denmark is in a low-selenium region of the world, and the Danish population as a whole has low selenium intakes and sub-optimal blood selenium levels. Danish researchers have, accordingly, investigated the association between pre-diagnostic selenium levels and the risk of total, advanced, and high-grade prostate cancer. Pictured here: the Dannebrog, Denmark’s national flag.

Higher blood selenium concentrations and higher blood selenoprotein P concentrations are significantly associated with reduced risk of high-grade prostate cancer [Outzen].

The researchers defined “advanced” prostate cancer as ≥T3 or with a Gleason-score ≥7.  They defined “high-grade prostate cancer” as cancers having a Gleason score equal to or greater than 8.

Furthermore, in survival analyses, a higher pre-diagnostic level of plasma selenium is significantly associated with a lower risk of all-cause mortality in prostate cancer patients [Outzen].

Selenium and prostate cancer in the “Diet, Cancer, and Health” cohort

These are the conclusions from an analysis of the data from the Danish “Diet, Cancer, and Health” cohort.  The cohort consists of 27,179 men living in the greater metropolitan areas of Copenhagen and Aarhus who were recruited into the study.  They were aged 50 – 64 years and had no previous record of cancer at the time of recruitment [Outzen]. read more

Selenium and prostate cancer: the toenail evidence

Meta-analyses have shown an inverse association between plasma/serum selenium concentrations and the risk of prostate cancer. The same inverse association has also been seen in three high-quality studies of toenail selenium concentrations and the risk of prostate cancer. The data from the Netherlands Cohort Study clearly show that higher toenail selenium is associated with significantly reduced risk of prostate cancer.

Analysis of data from the Netherlands Cohort Study shows that higher toenail selenium concentrations are associated with a substantial reduction in the risk of advanced prostate cancer.  Men in the highest quintile of toenail selenium had a statistically significant (p=0.001) 63% reduced risk of advanced (stage III-IV) prostate cancer compared to men in the lowest quintile of toenail selenium [Geybels].

Men in the highest quintile of toenail selenium concentrations had a toenail selenium level higher than 0.617 micrograms of selenium per gram of toenail.  Men in the lowest quintile of toenail selenium concentrations has a toenail selenium level lower than 0.469 micrograms of selenium per gram of toenail [Geybels]. read more