Selenium may prevent esophageal cancer

Selenium may inhibit progression toward esophageal cancer among people with the precancerous condition Barrett's esophagus, according to a new study.

Researchers in the US found that Barrett's patients with low blood selenium levels were two to three times more likely to experience advanced precancerous changes than patients with medium or high selenium levels.

A team from the Fred Hutchinson Cancer Research Center and University of Washington School of Medicine studied the relationship between levels of selenium in the blood and changes in the lining of the esophagus that represent advancement toward cancer.

"Our research suggests that low blood levels of selenium are a risk factor for progression of Barrett's oesophagus,"​ said Rudolph, an epidemiologist and clinical researcher in Fred Hutchinson's Public Health Sciences Division and lead author of the study.

However she cautioned that taking high doses of the trace mineral would not prevent the disease. "When it comes to selenium and Barrett's, there appears to be a law of diminishing return. More selenium is not necessarily better. In fact, laboratory studies indicate that high doses of selenium can be toxic and could even promote cancer, so 'megadosing' with selenium supplements is a bad idea,"​ Rudolph said.

The US recommended dietary allowance for selenium is 55 micrograms (mcg) for adults, while the UK's Expert group on Vitamins and Minerals recently recommended no more than 0.35mg in daily supplement intake. The average multivitamin is thought to contain up to 20 mcg. Fish, meat and nuts are also good sources, while bread tends to have much less in Europe than in the US, due to lower levels of the mineral in the soil.

Previous randomised clinical trials in humans have shown that selenium significantly reduces risk and mortality for multiple cancers, including prostate and colorectal. It has also recently been shown to inhibit skin cancer. The mineral is thought to inhibit the changes that cause cells to become cancerous. It has been found to slow abnormal cell growth, prevent DNA damage and facilitate the normal process of cell death, or apoptosis. Selenium is also known to act as an antioxidant, so it may interfere with the cell-damaging effects of free radicals produced during normal cell metabolism.

There is currently no proven, recommended medical therapy for lowering cancer risk in people with Barrett's, and while only 5 per cent to 10 per cent of Barrett's patients develop cancer of the esophagus, if it is not diagnosed early, the outlook is grim, according to researchers. The incidence is also rising faster than that of any other cancer in the United States.

"This research gives us hope that we will be able to develop medical means by which to lower Barrett's-related cancer risk and perhaps even reverse the risk among people who already show signs of progression toward esophageal cancer,"​ said Rudolph.

For the study, Rudolph and colleagues analysed data from 399 people with Barrett's esophagus and found that those with higher concentrations of selenium in their blood were less likely to have as many biological markers of progression towards cancer than those with less circulating selenium.

Those with higher levels of selenium were less likely to experience precancerous changes such as dysplasia - abnormalities in cellular size, shape or growth pattern; loss of heterozygosity at 17p - partial loss of chromosome 17, which can inactivate the tumour-suppressor gene p53, a gene that is critical for controlling cell growth; aneuploidy - the accumulation of cells with grossly abnormal amounts of DNA, which indicates substantial genetic damage and is a sign of advanced progression towards cancer; and increased 4N fraction - an excessive number of cells with twice the normal amount of chromosomes, which may indicate a problem with cell division.

Most significantly, the researchers found that higher blood levels of selenium were associated with a three-fold decreased risk of aneuploidy and a two-fold decreased risk of cellular dysplasia and loss of the p53 gene.

Selenium appeared to have the greatest effect on markers associated with advanced progression of Barrett's, which suggests that the nutrient might be most beneficial for people with later-stage disease, they reported.

"While blood levels of selenium weren't associated with one of the earliest markers of Barrett's progression, people with selenium levels in the middle or upper range of normal were less likely to have advanced precancerous changes than those with lower selenium levels,"​ Rudolph said.

Rudolph and colleagues noted that selenium might reduce Barrett's-related cancer risk by preventing the inactivation of the p53 tumour-suppressor or preventing further progression towards cancer after the gene has been shut off.

While the results are promising, more research is needed, Rudolph said. A limitation of the study is its cross-sectional design; the analysis was based on data collected from Barrett's patients at a single point in time, representing an isolated snapshot of biological activity.

"Following these same people over time eventually will give us a stronger understanding of how selenium and other dietary factors affect precancerous progression,"​ Rudolph said. "If the results of our study are confirmed in longitudinal studies and randomised controlled trials, the public-health impact could be substantial,"​ she added.

The study will appear in the May 21 issue of the Journal of the National Cancer Institute​.