One of the most common cancers and a major contributor to cancer-related death in males globally is prostate cancer (PCa) [1], which has a complicated etiology that includes both environmental and genetic components [2]. The rate of prostate cancer is rising in Iraq, with age-standardized figures showing 8.2 cases for every 100,000 men as per the latest GLOBOCAN statistics. This is concerning for the country as this number is on the rise. The Iraqi population stands out as having Middle Eastern ancestry, which might have unique genetic traits unlike those of either European or Asian populations. Very little work has been done looking at inflammatory gene polymorphisms in the Iraqi population, focusing mostly on the variants of other tumors. This demonstrates the need for genetic research focused on specific populations. Emerging evidence suggests that prostate carcinogenesis may be caused by chronic inflammation [3]. Interleukins (ILs), which are important mediators of inflammatory responses, have been related to angiogenesis, invasion, apoptosis, and proliferation of cells in the Cancer development [4]. Ethnic differences or polymorphism of a single base pair change within the nucleotide sequence interleukin genes alterations could lead to its expression and change in activity. This could alter the inflammatory milieu predisposing an individual to cancer ILs of interest include IL-1, IL-6, IL-10, IL-16, and IL-28 which are interleukins that have been advanced and associated with the immune response and prostate cancer [5], [6], [7]. These specific polymorphisms were selected due to their functional relevance to cytokine expression, as well as being located in promoter regions which control transcriptional activity and inflammation. IL-1β is a cytokine known for causing inflammation. It is involved in various inflammatory responses and associated with the onset and progression of tumors. The IL-1β gene has several genetic variants associated with different tumors and the rs16944 (-511C>T) variant located in the gene's promoter region influences transcriptional activity and has been associated with breast cancer as well [8], [9].

IL-6 is an example of a multifunctional cytokine with both pro-inflammatory and anti-inflammatory activity. In particular, it activates the JAK/STAT signaling pathway, which is important for cell growth and survival [10]. The rs1800795 (-174 G>C) polymorphism in the promoter region of IL-6 changes its expression levels and has been studied regarding its impact on prostate cancer risk with contradictory results [11], [12]. As for the role of IL-10, it acts as an anti-inflammatory cytokine and reduces the synthesis of pro-inflammatory cytokines. It may act in two ways in cancer: by promoting immune evasion, it can inhibit anti-tumor immunity, but it can also enable the lack of inflammation-driven tumor development[13]. The rs1800896 (-1082 G>A) polymorphism influences IL-10 production and has been linked to several types of cancer [14]. IL-16 acts as a chemoattractant for CD4 + T cells and is involved in the regulation of inflammatory responses. The rs4778889 (-295 T > C) variant in the promoter region of IL-16 has been linked to changes in gene expression and the risk of cancer [15], [16]. IL-28B (also referred to as interferon-λ3) exhibits both antiviral and immunomodulatory properties. The rs12979860 (C>T) variant has mostly been investigated in association with hepatitis C virus infections, but it has recently attracted interest in the field of cancer research [17], [18].

Prior investigations remain inconclusive concerning interleukin polymorphisms and risk of developing prostate cancer. In particular, the association of IL-6 −174 G>C showed protective (OR=0.68) and risk-increasing (OR=1.34) effects in European and Asian populations, respectively, suggesting population-specific influences. Also, IL-10–1082 A>G showed inconsistent associations in different ethnic populations underscoring the need for targeted verification studies. Although many studies have explored the links between specific interleukin gene polymorphisms and the risk of cancer, there is a lack of thorough analyses that consider multiple interleukin gene polymorphisms and their joint impact on susceptibility to prostate cancer. Additionally, findings from various populations have shown inconsistencies, highlighting the necessity for further research [19], [20], [21]. The main hypothesis of this research is that certain polymorphisms in the interleukin genes (IL-1, IL-6, IL-10, IL-16, and IL-28) are linked to a higher risk of prostate cancer among the Iraqi population.

Consequently, this case-control study was designed to explore the relationships between polymorphisms in the IL-1β (rs16944), IL-6 (rs1800795), IL-10 (rs1800896), IL-16 (rs4778889), and IL-28B (rs12979860) genes and the risk of prostate cancer, in addition to evaluating the cumulative effects of these polymorphisms via haplotype analysis.