Evaluation of some proinflammatory cytokines and biochemical parameters in pre and postmenopausal breast cancer women

After lung cancer, breast cancer is the second most common cancer worldwide, with 2,09 million cases in 2018.Around 1.9 billion adults were overweight and more than 650 million of them were obese during 2016. An important association exists between the risk of breast cancer and obesity. Premature menopause and premenopausal obesity decrease the risk, while postmenopausal obesity raises the risk because adipose tissue functions after menopause as the main reservoir for estrogen biosynthesis. Elevated serum estrogen levels and increased development of estrogen at the peripheral site have been seen as significant factors for developing breast cancer in postmenopausal women who are overweight [18]. Except for women with a family history of this condition, overweight and obesity are known to have a protective impact for premenopausal breast cancer; Therefore, body fat can be a strong indicator of improvement in breast cancer risk in postmenopausal women above BMI or weight, but the distribution of body fat can also affect the danger of breast cancer(Cleary and Grossman., 2009). Interleukin (IL)-6 has emerged as key compound significantly produced by breast cancer cells and adipocytes, with the potential of inducing proliferation, epithelial mesenchymal phenotype, stem cell phenotype, angiogenesis, cachexia, and therapeutic resistance in breast cancer cells [9]. IL-6 can influence all aspects of the tumorigenesis process by regulating proliferation, apoptosis, metabolism, survival, angiogenesis, and metastasis. [15]. Breast cancer(BC) is frequently preceded by inflammation operation characterized by the existence of tumor necrosis factor (TNF-alpha) as proinflammatory cytokines, which have a direct effect on the progression of the illness. Inflammation has been described mainly as a favorable condition for tumor progression. TNF- α can promote signals of stimulation, differentiations, survival or cell death, so the variants of this cytokine, its receptors, the presence of polymorphism and their implications for different phenotypes of breast cancer are essential to study. In this is way, in the treatment of breast cancer, TNF alone or in combination with chemotherapy and radiotherapy can serve as an adjuvant. [17].In the resent study C-reactive protein (CRP) is a representative marker for inflammatory conditions, and performs a crucial anti infection function in the immune system. In many cancers, it has been reported that chronic inflammation is involved with malignant change, and the risks of cancer are increased when pre-diagnostic CRP levels are high [7]. Cancer invasion begins with inflammation around cancer cells. Thus, it has been reported that serum CRP levels are higher in cases of invasive cancer than in cases of non-invasive cancer [22], [20]. CRP is generated by the liver and other organs in response to the release of IL-6 by monocytes and other immune cells. Thus, when IL-6 levels increased, CRP levels also increased. This has been proven by the positive association between IL and 6 and CRP in this study [21]. Lactate dehydrogenase (LDH) is the enzyme responsible for the conversion of pyruvate to lactate during glycolysis [3]. It is expressed in all tissues and its A and B subunits, coded by two different genes LDH-A and LDH-B, [4]. Elevated LDH levels are seen in cancer patients, and its prognostic value has been shown in several malignancies such as germ cell tumors, lymphoma, melanoma and renal cell carcinoma [12]. Gamma-glutamyltransferase (GGT) is a cell-membrane bound enzyme [16], GGT is responsible for the glutathione (GSH) metabolism, catalyzing the degradation of extracellular GSH and further promoting amino-acid recovery for subsequent intracellular GSH synthesis [2]. Intracellular GSH acts as an antioxidant, neutralizing free radicals and so plays a decisive role in protection against oxidative stress during cell metabolism. Therefore, GGT and GSH are increasing in circumstances of oxidative stress like carcinogenesis [5].However, analysis of the assessment of activity for lactate dehydrogenase, Gamma glutamyl transpeptidase and alkaline phosphatase in breast cancer has not yet been clear till now and many studies have tried to evaluate role of tumor markers in in diagnosis of carcinoma breast. The current study aim the possibility of using lactate dehydrogenase and Gamma glutamyl transpeptidase as screening tests among Sudanese women with breast cancer. [2]. While Bilirubin is a major product of heme catabolism, belongs to compounds with pleiotropic biologic effects. Although for decades it was considered as a metabolite dangerous for human health, recent data indicate that bilirubin exhibits potent antioxidant properties with substantial positive clinical consequences were also demonstrated, suggesting that bilirubin consumption during oxidative stress may belong to the major pathways, preventing deleterious effects of oxidative stress(Libor Vítek, 2005). Bilirubin is a potent antioxidant and has been shown to protect against cancer development. Lower serum bilirubin level has been linked to increased risk of cardiovascular diseases and cancer [19], [11]. An association between the risk of breast cancer and persistently elevated blood levels of estrogen has been found consistently in many studies. Several endocrine-associated risk factors are regularly associated with an increased relative risk of breast cancer in postmenopausal women.(Richardson and Johnston et al., 2003). Obesity, which may be associated with increased estrogen production in breast adipose tissue via aromatase activity, is one of these factors (Key et al., 2003). The elevated blood level of endogenous estrogen is another factor. (relative risk, 2.00 to 2.58). Higher-than-normal blood levels of androstenedione and testosterone, androgens that can be specifically converted to the estrogens estrone and estradiol via aromatase, are often correlated with an increased relative risk. An increased risk of breast cancer in postmenopausal women is also associated with elevated urinary levels of estrogen and androgen. (Onlandd-Moret et al., 2003). Vitamin D (Vit D) exerts a range of immunogenic and antiproliferative activities by its binding to receptors of vitamin D (VDR) found in the nucleus cells of the breast. [13]. This is why high confidence level Vit D levels could contribute to cancer development by impairing cell proliferation, differentiation, apoptosis, and angiogenesis. [1]. Interestingly, individuals with higher exposure to the sun, high intake, or high vitamin D sera levels have reported a decreased occurrence of breast, colon, and prostate cancers. [8]. The level of some minerals such as Calcium and phosphorus metals ion do not relate to the carcinogenesis process, but their elevated serum levels can be due to local and systemic changes in breast cancer. [23]. The association between free radicals and polyunsaturated cell membrane fatty acids induces lipid peroxidation and subsequent damage to cells. This contributes to intracellular phosphorus leaking into the serum. [14]. High blood calcium levels have been linked to peptide-related parathormone action, osteolytic bone metastasis, and elevated acid phosphatase levels in breast tumor tumors. [10]. The results of the current study highlight the role of these metal ions as compounding factors in breast cancer growth. As these metal ions play an important role through different pathways in carcinogenesis. While Uric acid is synthesized mainly in the liver, intestines and the vascular endothelium as the end product of an exogenous pool of purines, and endogenously from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine, are degraded into uric acid. Mentioning uric acid generates dread because it is the established etiological agent of the severe, acute and chronic inflammatory arthritis, gout and is implicated in the initiation and progress of the metabolic syndrome [6].Table 1.

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