Several potential biological mechanisms may connect Se to BC playing its role in human health through incorporation in selenoproteins.
Selenoproteins have a range of various functions in the body. Our study examined Se and selenoprotein status and BC diagnosis. The previous studies only analyzed these components’ differences in patients and healthy subjects. To our knowledge, this is the first study that has prospectively assessed levels of Se, SelP, and SelS in normal breast tissue, tumoral tissue, and serum concerning subsequent BC risk. Generally, serum measurements tend to reflect short-term exposures, while trace element levels in tissue cells represent long-term exposure; thus, we analyzed its level in both serum and tissues to decrease the short-term exposure errors [14, 15].
The current study found evidence of lower proportions of Se (65.99 µg/L) among breast cancer cases compared to age-matched controls. Interestingly, Charalabopoulos et al. also found low serum Se levels in women with BC compared to those in the control group. On the other hand, they have demonstrated that Se levels were twofold higher in the tumor tissues than in healthy breast tissues, implying that Se exerts regional effects, whilst no difference between Se levels in tumoral and normal tissues was found in our investigations [16].
Similar to us, other studies have revealed that Serum Se levels are inversely associated with the incidence of BC[6, 17–19]. In a meta-analysis of 8 studies in which Se concentrations were measured in serum, a significant correlation was observed between Se concentration and BC. Also, four case-control studies discovered that Se status in serum was notably lower among BC patients than in control subjects. The mean serum Se level among the BC cases in one study was 73.3 µg/L, which is substantially lower than that previously documented among women living in areas with high dietary Se intake [20]. The average serum Se for women aged 40 or older was 134.7 µg/L which is substantially higher than what we reported in this study (105.30 µg/L) [21, 22].This implies that our results may only be generalizable to other countries, and similar studies are repeated in such countries to validate our findings further. Also, a nested case-control examination of women revealed that low serum Se (≤ 70 µg/L) was associated with a two-fold increased risk of developing BC compared to those with Se levels between 70 and 90 µg/L [23]. Collectively, Multiple studies (in vivo and in vitro) have declared that Se may prevent cancer by affecting cell proliferation, apoptosis, oxidative stress, and immunity [19, 24].
On the other hand, Patients with low Se levels had high mortality risk. Prediction of mortality based on all three biomarkers exceeded tumor characteristics, including grade, lymph node numbers, and tumor length; so, Se status assessment at BC diagnosis identifies patients at extremely high risk for a weak prognosis [18]. However, no correlation between Se status and specific breast cancer characteristics was found in our research, indicating that Se might be an independent prognostic factor for BC mortality as well as Charalabopoulos et al., results [16].
Thus, the decrease in serum Se proportion is of outstanding significance. These alterations may reflect a piece of the defense mechanisms against the cancer process.
Besides, Selenoproteins are potent carcinogenesis and tumor progression modifiers, inhibiting tumor growth by revoking oxidative stress, particularly in cancers those inflammatory mediator’s drive. BC is a chronic inflammatory condition with raised oxidative stress and changed redox homeostasis. Low selenoproteins levels lead to inflammatory responses, which may progress to BC [25]. Circulating SelP seems to fulfill the requirements for a Se status biomarker, reaching maximal proportions of 5–7 mg/L at intakes of 100–150 µg Se per day. Our study also measured a SelP level of 4 mg/L, which was substantially lower than in controls [26]. However, there was not any relationship between age and SelP level. Similar to us, in Bordin et al., study it has been revealed that age is not related to the SelP status [26].
Also, Ekoue et al. demonstrated that associations between Se status and SelP levels were obtained in the breast tissue samples [27], which in our study we have found out the same results in both tissue samples. Also, as well as our observations, in Bordin et al, investigation, Se and SelP concentrations were correlated tightly at the baseline and increased in parallel [26]. In a cohort of the German prostate cancer population, a strong correlation between total Se and SelP levels in serum samples has been found. Meyer et al. found that decreased Se correlates with SelP levels with higher tumor grade. However, there was a lower serum level of total Se and SelP in patients than in men with NEM [28]. Also, a positive association between plasma SelP concentration and lung adenocarcinoma risk has been found. Previously, similar positive associations between SelP and other chronic diseases such as type 2 diabetes and esophageal adenocarcinoma were reported, with a suggestion of SelP as a prognostic marker of a disease rather than a risk factor [29, 30].
Our results have shown a significant difference between SelP levels in serum and tissues whilst no difference between SelP levels in tumoral and normal tissues was found. In addition, another US study did not find differential associations between SelP concentration and lung cancer risk. Although cases appear to have a slightly lower SelP concentration in pre-diagnostic plasma than in controls, there was no association between plasma SelP concentration and lung cancer risk and tumor aggressiveness [31].
In contrast, another research demonstrated no association between Se and SelP levels or their combined prostate cancer score, risk, grade, or stage. After adjusting for multiple testing, Selenoprotein is not associated with prostate cancer risk. However, the association between plasma Se, SelP, and high-grade PC risk in a nested case-control study has been revealed [32]. In the following, studies revealed a lack of association between SelS level and BC incidence. To our knowledge the investigations are focusing on SelS expression and its variants around different cancers. It has been revealed that variations in the SelS promoter sequence are associated with susceptibility to inflammation-related diseases [33]. SelS is widely expressed in a variety of tissues and has its characteristic expression. It may affect the function of resisting tumors when the SelS gene mutates [34]. However, there is a significant association between SelS rs34713741 gene polymorphism and gastric cancer[34]. In another study of a Japanese population, it has been demonstrated that the − 105G > A polymorphism of the SleS1 gene is associated with increased risks of the intestinal type of gastric cancer [35, 36]. Also, one report showed non-significant differences in SEPS1 allele frequencies between young stroke patients and healthy controls [37]. Besides, other research has shown that GPX1, GPX4, and SelS are overexpressed explicitly in TNBC cells and tissues. The overexpression of SelS is correlated with advanced stages and poor prognosis in BC tissues, representing a novel potential prognostic signature and a therapeutic target to be exploited in BC [38]. However, we found that SelS status in patients’ serum (1353 ng/ml) is lower than in the age-matched controls. However, a weak negative correlation between serum and tissue proportions of SelS has been found, which needs more investigation.