Colorectal cancer (CRC) is ranked as the fourth among all types of cancer leading to death and it is the third most commonly diagnosed type of cancer [1]. Every year between one to two million new cases are diagnosed world-wide. Most of the cases of CRC are being detected in the Western countries (55%) although over the past few years, the scenario is changing in Asian countries as well owing to the fast development of some countries and adaptation of Western diet and sedentary lifestyle. It is estimated by the year 2035 the total number of deaths from rectal and CRC will increase by 60% and 75%, respectively [2].

It has been well established that disturbances in the concentration of some trace elements may lead to cell damage, DNA damage and imbalance in oxidative stress burden [3], [4] eventually leading to malignant transformation [5]. In the last few years, there have been extensive studies for understanding the exact role of trace elements in the pathogenesis of many cancers including CRC [3].

Selenium (Se), a naturally occurring element, is an important trace element with relevant nutritional properties. It is a cofactor of the antioxidant enzymes glutathione peroxidase (GSH-Px) and thioredoxin disulfide reductase which transforms thyroxine into triiodothyronine [6]. However, high level of Se (selenosis) is associated with type 2 diabetes [7] and lung cancer [8], whereas low levels of Se has been found to be associated with increased risk of other different types of malignancy, including CRC [7], [9]. The Se containing proteins (selenoproteins) have been found to have a wide range of pleiotropic effects which include anti-inflammatory and antioxidant properties [7]. In addition, Se controls the expression of some oncogenes and facilitates the activity of the immune system. There is still limited knowledge on the expression of selenoproteins in CRC or on their interplay with Se status [10].

Furthermore, in a seminal study, Cornish AJ et al., 2020 have reported a suggestive association between increased serum Se levels and decreased CRC risk (ORSD 0·85 [95% CI 0·75–0·96]; p=0·0078), but this association was based on only one single nucleotide polymorphism [11]. In concurrence, another study concluded that low levels of Se increased the risk of CRC [12]. Based on the above facts, it will be interesting to evaluate the Se levels in CRC which might be helpful to provide a platform for future studies to study the underlying molecular mechanism which in turn might be helpful in the prevention and treatment of CRC.

A 2017 systematic review on Se in CRC including 11 studies (7 serum and 4 colon tissue specimen studies) showed that serum Se levels were lower in CRC than in control subjects. Furthermore, the same study reported inconsistent results regarding Se levels in malignant with respect to non-malignant tissue specimens [13]. As the number of published studies on Se in CRC has increased since then, the current Systematic Review and Meta-Analysis (SRMA) is timely and could help define a clear role for Se in CRC.