Selenium and colorectal cancer: The Bonelli study

Dr. Luigina Bonelli and a team of researchers in Genoa, Italy, were motivated by the following set of compelling facts:

• Colorectal cancer was the second leading cause of cancer death in Europe.
• Adenomas in the colon (adenomas are benign tumors, which sometimes transform to malignant tumors) were known to be precursors of colorectal cancer.
• Patients who had undergone a colonic polypectomy (removal of an adenomatous polyp) had an increased risk of developing colorectal cancer and needed to have periodic follow-up colonoscopies.
•  Increased risk of developing adenomas was equated with increased risk of developing colorectal cancers.
•  Observational studies indicated that there was an association between the plasma or serum concentrations of several antioxidant substances including selenium and the risk of colorectal cancer.
•  In some intervention studies, supplementation with selenium was associated with reductions in the incidence of colorectal cancer.

The time was right to start a large study of the effectiveness of selenium and other antioxidants in reducing the risk of colorectal cancer.

Selenium to reduce the risk of colorectal cancer
Dr. Bonelli and her colleagues wanted to see if daily supplementation with a combination of antioxidants including selenium could reduce the risk of recurrent adenomas in patients who had had one or more adenomatous polyps removed.  The researchers designed a randomized, double-blind, placebo-controlled clinical trial and, over the period of many years, they enrolled a total of 411 patients who had undergone a polypectomy.

Selenium and antioxidants versus placebo
In the Bonelli study, the patients were randomly assigned to receive the active treatment or a matching placebo treatment.  The active treatment consisted of daily supplementation for a five-year period with the following compounds:

• 200 micrograms of selenium
• 30 milligrams of zinc
• 2 milligrams of vitamin A
• 4.4 milligrams of vitamin B6
• 180 milligrams of vitamin C
• 30 milligrams of vitamin E

Dr. Bonelli writes in her report in the Journal of Gastroenterology (2013) that “the active compound and the placebo had an identical appearance and were provided by Pharma Nord (Denmark). The assigned treatment was intended to be taken for 5 years” or until the recurrence of an adenoma.  The selenium component of the active treatment was an organic selenium preparation.

The outcome of the selenium and antioxidant supplementation: 39% risk reduction
During the course of the study, the researchers did follow-up colonoscopies on 330 of the study participants: 164 in the active treatment group and 166 in the placebo group.  Of the 330 patients, 100 had had a recurrence of an adenoma.

38 of the recurrences took place in the active treatment group, and 62 of the recurrences took place in the placebo arm. There was, accordingly, a 39% reduction in the risk of recurrence that could be attributed to the active intervention with selenium and zinc and antioxidant vitamins.

Similar outcomes for two types of adenomas
Interestingly, the risk reduction was similar and significant for both small tubular adenomas and advanced adenomas.

Conclusions about selenium and adenomas and colorectal cancer
The Bonelli study was a carefully designed clinical trial structured in such a way as to eliminate the influence of bias on the outcome (recurrence of adenomas in the colon).

The study provided statistically significant evidence that antioxidant supplementation with selenium as the primary component reduces the rate of adenoma recurrence.  Because adenomas are known to be precursors to colorectal cancer tumors, the researchers recommended that additional clinical trials address the role of selenium and other antioxidants in various sub-groups of individuals deemed to be at increased risk for colorectal cancer.

Recommended future research
The researchers recommended more research of the effect of selenium and other antioxidants on various sub-groups.  For example, is the active treatment with selenium more effective with smokers than with non-smokers, more effective with male participants than with female participants, more effective with participants with below normal baseline selenium status than with participants with normal baseline selenium status?

Furthermore, it would be interesting to find out whether supplementation with selenium alone has the same statistically significant effect on the incidence of colorectal adenomas as the treatment with selenium and a combination of antioxidants had in the Bonelli study.

Conclusion
The Bonelli study was a randomized controlled study that showed that supplementation with selenium and other common antioxidants can significantly reduce the risk of developing colorectal cancer.

Postscript: In 2015, Dr. David Hughes at the Royal College of Surgeons in Ireland, together with research colleagues across Europe, investigated the effect of selenium status on the risk of colorectal cancer in a nested case-control study with 966 colorectal patients and 966 matched controls. The researchers’ findings indicated that blood selenium levels and blood selenoprotein P levels are sub-optimal in the adult residents of many European countries; their findings suggested further that there exists an inverse association between the risk of colorectal cancer and higher blood selenium status.  The inverse relationship between colorectal cancer risk and blood selenium status was more evident in women.

In 2013, Lener et al  did a study of 169 colorectal patients and 169 controls.  They found a strong significant association between low selenium level and the colorectal cancer risk.

Sources:

Bonelli, L., Puntoni, M., Gatteschi, B., Massa, P., Missale, G., Munizzi, F., & Bruzzi, P. (2013). Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. Journal of Gastroenterology, 48(6), 698-705.

Hughes, D. J., Fedirko, V., Jenab, M., Schomburg, L., Méplan, C., Freisling, H., & … Hesketh, J. E. (2015). Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. International Journal Of Cancer, 136(5), 1149-1161.

Lener, M. R., Gupta, S., Scott, R. J., Tootsi, M., Kulp, M., Tammesoo, M., & Lubiński, J. (2013). Can selenium levels act as a marker of colorectal cancer risk? BMC Cancer, 13214.