Breast cancer is the most prevalent cancer in women at present, yet its cause is still not understood. On the other hand, the role of cytokines in the defense mechanisms of the body against cancer and cancer growth is well known. Some authors have considered inflammation as a principal indicator of initiation and progression of cancer (7, 30). It appears that certain changes associated with cancer, oxidative stress and free radicals could have a significant influence on the start of inflammation (31, 32). Recently, different genetic polymorphisms have been evaluated as genetic indicators in the process of development and progression of complex and prevalent diseases such as cancer. Multiple polymorphisms of IL-10 gene have been recognized and their association with BC and its progression have been evaluated so far. IL-10 is joint with numerous molecules as a multi-functional cytokine (Fig. 2) and could have either tumor enhancer or suppressor through exerting immune suppression and anti-angiogenic properties (33).
In this study, we looked at the connection between rs1800782 polymorphism and breast cancer in regard to the three functional polymorphisms contained in the IL-10 gene. Our data demonstrated enhanced risk of BC with this polymorphism which is located on promoter region of this gene. This polymorphism exerts a fundamental role in the clinical course of BC through influencing gene expression. Several studies confirm these data. Dai et al 2014, reported enhanced risk of BC with the recessive model of this polymorphism (33). However, data regarding rs1800782 polymorphism with BC are controversial. Tian et al, 2017, demonstrated diminished rate of BC with rs1800782 polymorphism (26). Langsenlehner et al in 2005 observed the same results, too (34). The mechanism of this effect is yet unclear, but it could be related to the tumor escape mechanisms through immune suppression using IL10. In other similar investigations, these associations were not confirmed (35). By the way, there are scant data regarding the association between this polymorphism and BC in central region of Iran. Different results derived from various studies could be due to racial and geographic differences and environmental factors.IL10 is considered as a pleotropic anti-inflammatory cytokine that exert its anti-carcinogenic effects in various neoplasms through activating natural killers (NKs) and prevention of angiogenesis and or other mechanisms especially in BC (21). Further studies showed that a number of cytokines, for example IL-6, IL-8, IL-12, IL-18, TNFα, IL-1α and IL-1β, could be hindered from progressing the tumor, which is a major factor in eliminating cancerous cells (36, 37). Besides, it also impacts on antigen presenting cells (APCs) which prevents differentiation of Th1 and Th2 cells with subsequent prohibited production of their related cytokines. This indicates to the role of IL-10 in facilitation of escape from cancer immunity (18). A binding complex composed of IL-10R1 and IL-10R2 - both belonging to the class II receptor family - allows the connection of IL-10 to its receptors. This consequently triggers the tyrosine kinases JAK1 and TyK2, which are linked to IL-10R1 and IL-10R2, to phosphorlate a tyrosine amino acid located inside of IL-10R1. Subsequently, the phosphorylation of this tyrosine causes an increase in STAT-3 transcription factor expression. After IL-10 binds to its receptors, the STAT-3 becomes quickly and continuously activated, allowing a longer period of phosphorylation compared to the short phosphorylation phase of STAT-3 caused by IL-6 activation (38). There is evidence that the interaction between SOCS3 and STAT-3 has an influence on the production of IL-10. Experiments have confirmed that decreased STAT-3 levels result in significantly diminished IL-10 output, whereas silencing SOCS3 brings about an increase in IL-10 generation (39).
Depending on its position within a gene, one nucleotide variation may have an impact on gene expression, the assembly of RNA, the process of joining sections of a ribonucleic acid molecule, and how a protein performs its function (40–42). Examining the consequences both inside and outside of the laboratory of genetic variations on gene performance consumes a lot of time and money. However, applying computational methods could be useful in this regard (43–45). Since rs1800782 polymorphism is located on IL-10 gene promoter, it could impact on gene expression. Our exploration on rs1800782 of IL-10 gene indicated a link between this polymorphism and an augmented vulnerability to BC. Consequently, this variability might serve as a genetic biomarker for recognizing susceptive subjects. Still, research involving a greater number of people from different racial backgrounds must be completed in order to obtain incontestable data. Environmental facets such as location, the collective being evaluated, sample mass, entry and exemption criteria, and so on, all have an influence on research regarding polymorphisms.