Selenium and oral cancer

Because many cancers take so long to develop, research studies with cancer as the endpoint require a long period of observation and are very expensive. Focus on intermediate endpoints such as bio-markers for the development of cancer are useful for assessing the value of  selenium supplements for cancer prevention. Pictured here: a histo-pathologic image showing squamous cell carcinoma in a biopsy specimen.

When we test the efficacy of selenium supplementation in the prevention of cancer, we often look at the effect of the selenium supplementation on bio-markers for the development of cancer.  Bio-markers are substances whose presence in blood or tissue indicates the concurrent presence of a disease or an infection.

An Indian (sub-continent) research study has shown that supplementation with selenium, zinc, riboflavin, and vitamin A significantly inhibits the development of bio-markers for oral cancers [Prasad].

Okay, because the selenium was administered as one component in a micro-nutrient cocktail, we cannot attribute the outcome solely to the selenium supplementation.  But it is a good bet that the selenium – through its incorporation into antioxidant selenoproteins – was a major factor in the beneficial health effects.  There is support for the idea that antioxidant supplements are effective cancer chemopreventive agents [Prasad].

Selenium and cancer in the mouth

Researchers at the Indian Council of Medical Research in Hyderabad, India, wanted to see if the administration of selenium and other micronutrients would reduce the number of lesions and the frequency of two bio-markers for oral cancer in smokers.

The research results showed the following significant reductions:

  • total regression of lesions (wounds, ulcers, abscesses) in the mouth in 57% of the smokers receiving the active supplement treatment and in only 8% of the smokers on the placebo treatment [Prasad]
  • further progression of existing lesions occurred in only 10% of the supplemented group compared with 47% in the placebo group [Krishnaswamy]
  • appearance of new lesions in the mouths of only 12% of the smokers on the active supplement treatment but in 48% of the smokers on the placebo treatment [Prasad]
  • 60% reduction in the frequency of micronuclei in the mouths of smokers with and without lesions who received the active supplement treatment compared with 35% reduction in the mouths of smokers who received the placebo treatment [Prasad]

Moreover, all of the reductions in the frequency of micronuclei in the smokers in the placebo group occurred in the smokers without lesions in the mouth.  None of the reductions in the placebo group occurred in smokers with sores in their mouths.

Note: Micro-nucleated cells are cells that develop whenever a chromosome or part of a chromosome does not get incorporated into the daughter cell during cell division. These micronuclei are often seen in cancer cells.

The Indian study also showed significant results with respect to DNA adducts:

  • Thirteen-fold greater reduction in the number of DNA adducts in the active supplement group than in the placebo group for smokers with lesions in their mouths
  • Three-fold greater reduction in the number of DNA adducts in the active supplement group than in the placebo group for smokers without lesions in their mouths [Prasad]

Note: DNA adducts are segments of DNA that are bound to cancer-causing substances.  As such, they are bio-markers for the development of cancer, in this case, cancer in the mouth.

The participants in the selenium and precancerous lesions study

The Indian researchers enrolled a total of 298 smokers: 79 males and 219 females between the ages of 25 and 70 years.  Two-thirds of the study participants had precancerous lesions in their mouths; one-third did not.

The study participants were smokers of unprocessed tobacco wrapped in semi-dried tobacco leaves (the cigarettes are known as beedis; the tobacco is called chutta).  The smokers smoked the cigarettes with the lit end in their mouths, in a process known as “reverse smoking” [Prasad].  Chutta smoking is associated with high rates of oropharyngeal cancer [Malik].

The study participants were assigned randomly to a supplement treatment group (n=150) and to a placebo control group (n=148).  The researchers did a complete oral examination initially and again after twelve months of participation.  They removed and examined oral epithelial cells from the mouths of the participants for the presence of DNA adducts and micronuclei.

Note: The epithelial cells referred to here are the cells that line the inside of the mouth and the esophagus.

The dosages used in the selenium and oral cancer study

The study participants took the antioxidant supplements or the placebo in a single capsule twice a week for an entire year.

  • During the first fourth months of the study, the participants in the active supplement group received 100 micrograms of selenium and 12.5 milligrams of zinc per tablet.  During the last months of the study, the dosages were changed to 50 micrograms of selenium and 25 milligrams of zinc.
  • The dosages of riboflavin varied accordingly: 50 milligrams during the first four months followed by 15 milligrams during the second four months and, finally, 30 milligrams during the last four months of the year-long study.
  • Vitamin A dosages were 25,000 international units during the first and last four months of the study and 10,000 international units during the middle four months.

In other words, the dosages used were physiological dosages, not pharmaceutical dosages.

Scientific information from the selenium and oral cancer study

The data of the Indian research study show the following encouraging outcomes:

  • The two bio-markers for the development of cancer of the mouth – DNA adducts and micronuclei – were reduced significantly by the administration of selenium and the other antioxidant nutritional supplements.
  • The number of lesions in the mouths of smokers was reduced, the progression of existing lesions was reduced, and the development of new lesions was decreased significantly by the administration of selenium and other antioxidant nutritional supplements.
  • The positive clinical response of the participants to the antioxidant supplement treatment in terms of cancer bio-markers and precancerous lesions suggests a beneficial impact in the prevention of the development of full-blown oral cancer.

Note: What do we mean when we say that the association of the selenium supplementation with a beneficial health outcome was statistically significant?

We mean that the probability is very small that we would get a health benefit of the selenium supplementation as large as the one we got, compared to placebo, merely because of chance or because of sampling variability.  In this Indian study, the probability of getting the observed association between selenium supplementation and the reduction in frequency of micronuclei was less than one chance in a thousand.  Our uncertainty about the “truth” of the observed health effects is correspondingly low.

Sources

Krishnaswamy, K., Prasad, M. P., Krishna, T. P., Annapurna, V. V., & Reddy, G. A. (1995). A case study of nutrient intervention of oral precancerous lesions in India. European Journal of Cancer. Part B, Oral Oncology, 31B(1), 41-48.

Malik, S. K., Behera, D., & Jindal, S. K. (1983). Reverse smoking and chronic obstructive lung disease. British Journal of Diseases of The Chest, 77(2), 199-201.

Prasad, M. P., Mukundan, M. A., & Krishnaswamy, K. (1995). Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity. European Journal of Cancer. Part B, Oral Oncology, 31B(3), 155-159.

Disclaimer: The information presented in this review article is not intended as medical advice and should not be used as such.

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