The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer
Introduction
Most cancers, including lung cancer, develop in a multistep fashion with specific genetic defects occurring in oncogenes and tumor suppressor genes during tumorigenesis. Such process may be influenced by environmental factors such as radiation and carcinogens as well as by intrinsic factors such as chronic inflammation or immunosuppression [1]. Epidemiological evidence suggested that pulmonary diseases with a prominent chronic inflammatory component could elevate the risk for lung cancer [2]. Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic functions and consequently has both tumor-promoting and tumor-inhibiting properties. Raised levels of serum and peri-tumoral IL-10 production have been reported in many malignancies [3], [4], [5], including lung cancer [6], which have been interpreted in support of a role for IL-10 in tumor escape from the immune response. Furthermore, increased production of immunosuppressive IL-10 by non-small cell lung cancer (NSCLC) and increased serum concentrations of IL-10 in NSCLC patients have both been shown recently to correlate with reduced survival [7], [8], [9].
IL-10 is encoded by a gene located on chromosome 1. The promoter spans a region of at least 5 kb upstream of the transcription start point and known to contain at least 27 polymorphic sites [10]. These polymorphisms include single nucleotide polymorphisms (SNPs) at -1082, -819 and -519, and at least two microsatellite repeats with several allelic forms [11]. Alterations in IL-10 expression have been linked to polymorphisms in the promoters of the IL-10 genes.. The homozygous AA allele at IL-10-1082, leading to a lower IL-10 expression [12], has been associated with several cancers, including advanced cutaneous malignant melanoma, breast cancer [13] and prostate cancer [14], while the higher producing genotype (GG) has been linked to cervical cancer [15].
As yet, the association between the IL-10 polymorphism with lung cancer susceptibility has not been reported in the literature. Therefore, in this study, we aimed to investigate the distribution of genotypes of the IL-10 in NSCLC patients and healthy controls with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the association of these polymorphisms with NSCLC susceptibility.
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Study population
Study cases included in this research were 154 patients of non-small cell lung cancer (NSCLC), including 93 adenocarcinomas (AD), 59 squamous carcinomas (SQ), and 2 large-cell carcinomas (LC), who admitted to China Medical University Hospital, Taichung, Taiwan, between 2002 and 2004. The histological classifications of types and stages of these tumors were conducted according to the WHO classification method (WHO, 1982) and the TNM system (Mountain, 1986), respectively. Meanwhile, 205
Results
A total of 359 individuals, including 154 NSCLC patients, including 106 males and 48 females with a median age of 63, together with 205 healthy controls, consisting of 136 males and 69 females with a median age of 62, were studied in this research. The characteristics, including age and gender of all participants in this study were summarized in Table 2. No significant differences in abovementioned features were observed between patients and controls.
The results of genotype frequencies of IL-10
Discussion
This is the first report to attempt to evaluate the association between the polymorphisms of the IL-10 promoter and lung cancer risk. The study of IL-10 gene transcriptional control is of interest because of the pivotal role of IL-10 in the regulation of the immune response system. IL-10 was originally termed as cytokine synthesis inhibitory factor due to its ability to inhibit synthesis of pro-inflammatory cytokines such as TNF-α, IL-I, IL-6 and IL-12 [16], [17]. IL-10 is also an important
Acknowledgement
This study was supported by a grant from Chung Shan Medical University (CSMU 88-OM-B-017).
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2021, Gene ReportsCitation Excerpt :The IL-10 cytokine in humans is coded by interlukin-10 (IL-10) gene, which is located on the chromosome 1 (1q31–32) and contains 5 exons (Eskdale et al., 1997). Numerous polymorphisms are reported on the IL-10 gene but clinically important three polymorphisms on the promoter region viz. -1082A > G (rs1800896), -819C > T (rs1800871) and -592C > A (rs1800872) have been extensively studied in different types of cancers like- breast (Li et al., 2020), lung (Shih et al., 2005), gastric (P. Kumar et al., 2015; S. Kumar et al., 2015), cervical (Datta et al., 2020; Pereira et al., 2020), and bladder cancer (Ahirwar et al., 2009). IL-10 may possibly increase tumor development, as it suppresses the anti-tumor immune response.
Genetic polymorphism of interleukin-10 (-A592C) among oral cancer with squamous cell carcinoma
2017, Archives of Oral BiologyCitation Excerpt :Our observations are supported by several earlier studies, where the IL-10 (-A592C) gene polymorphism has been reported to be significantly associated with the breast cancer, lymphoma, colon cancer, lung cancer, gastric cancer, non-small cell lung cancer (NSCLC) and ovarian cancer (Giordani et al., 2003; Kozlowski, Zakrzewska, Tokajuk, & Wojtukiewicz, 2003; Levy & Brouet, 1994; Pisa et al., 1992; Sugimoto et al., 2007; Zhang et al., 2015). There is an earlier report that in Chinese population alleles −592C were found to be significantly associated with the occurrence of NSCLC (Shih et al., 2005). Similarly, Zhou et al. (2014) also demonstrated that the IL-10 (-592) A/C gene polymorphism was significantly associated with the increased level of IL-10 in laryngeal squamous cell carcinoma (LSCC).
IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients IL-10 polymorphism and plasma levels in leukemia patients
2015, Blood Cells, Molecules, and DiseasesCitation Excerpt :Many studies have analyzed IL-10 polymorphisms and its expression in different models, like inflammatory, infectious, auto-immune diseases and cancer [12,13]. In cancer, these polymorphisms have been associated with increased risk in several types, including cervical [14], gastric [15], colorectal [16], B-cell lymphoma [17] and lung [18]. However, a study showed that IL-10-deficient mice had increased levels of Treg and MDSC, associated with tumor development [19], demonstrating a pleiotropic function of IL-10 in cancer.
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2024, Asian Pacific Journal of Cancer PreventionThe Involvement of Interleukin-10 Promoter Genetic Polymorphism in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma from North Africa
2022, Eurasian Journal of Medicine and Oncology
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These authors contributed equally to this work.