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  • K 252a br Pediatric Growth and Development Research Center

    2020-08-06


    5 Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
    6 Scientific Society of Evidence-Based Knowledge, Research Office for the History of Persian Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
    * Corresponding author: Farhad Shahsavar, [email protected]
    ACCEPTED MANUSCRIPT
    Abstract
    Objectives: This study was aimed to evaluate the disease association of each killer-cell immunoglobulin-like receptor (KIR) gene and their known human leukocyte antigen (HLA) ligands (HLA-C and -Bw4) as well as KIR haplotypes and KIR-HLA interactions in Lur population of west of Iran.
    Methods: In this case-control study, 50 cases with colorectal cancer and 100 healthy controls were taken. The genomic DNA was extracted and polymerase chain reaction with sequence specific primers (PCR-SSP) was used to genotyping the samples. Statistical analysis was done using 2 by 2 tables. In order to compare the results with other previous studies, funnel plot and cluster analysis was used.
    Results: Among the single gene analyses, only the association of KIR2DS5 was statistically significant (Pearson chi-square P =0.0206; Yate's corrected chi-square P =0.0323; OR =2.25 [1.12-4.49 95% CI]). No significant association was observed for neither KIR nor HLA genotypes. Among the KIR-HLA interactions, no significant association was observed as well.
    Conclusion: The results of this paper supported the results of previous studies as well as the rationale existing behind the tumor biology. The ligand of KIR2DS5 should be discovered and evaluated in future.
    Keywords: KIR, HLA, colorectal cancer
    ACCEPTED MANUSCRIPT
    1. Introduction
    Natural killer (NK) K 252a play a key role in human immunity. They express both activating and inhibitory receptors. One of their famous receptors are killer-cell immunoglobulin-like receptors (KIR). KIRs are expressed by the KIR genes which has a wide diversity and are inherited as haplotype. It means that the number and variety of these genes can be different among individuals. Of course in contrast to human leukocyte antigen (HLA) genes, existence of all genes of this haplotype is not necessary. KIRs have different known and unknown ligands. The known ligands are usually HLA-C and -Bw4 [1]. Colorectal is a common malignancy of both genders associated with inflammatory etiologies such as inflammatory bowel disease [2]. This cancer is highly genetic associated. Previously the association of genes like adenomatous polyposis coli (APC) and KRAS have been investigated a lot. However an anthropological approach to role of KIR and HLA genes in colorectal cancer should be regarded [3].
    In solid tumors, sustained angiogenesis is a hallmark [4, 5]. This phenomenon may have different causes like chronic inflammation in the microenvironment of solid tumors [6]. NK cells usually act against cancer cells through their cytokines; however these cytokines have angiogenic effect. Therefore it is not clear whether NK cell activation results in tumor suppression or progression [7, 8]. It seems that it may be different among different individuals and ethnicities because of a wide spectrum of polymorphic receptors and ligands. It shows the importance of personalized medicine in cancer diagnosis and treatment.
    ACCEPTED MANUSCRIPT
    This study is aimed to evaluate the disease association of each KIR gene and their known HLA ligands (HLA-C and -Bw4) as well as KIR haplotypes and KIR-HLA interactions in Lur population of west of Iran. In addition we intend to compare this study with previous studies numerically (a meta-analytical approach).
    ACCEPTED MANUSCRIPT
    2. Methods
    This work was an association study with a case-control design with regional and single center data. The study was performed according to strengthening the K 252a reporting of observational studies in epidemiology (STROBE), strengthening the reporting of genetic association studies (STREGA) and strengthening the reporting of immunogenomic studies (STREISS) guidelines [9, 10].
    This work was done in Shahid Rahimi hospital, Lorestan province, Khorramabad, west of Iran. The samples were taken during 2017.
    2.3. Participants
    A number of 50 cases with colorectal cancer and 100 healthy controls were taken. The eligibility criteria for the cases were known cases of colorectal cancer without any autoimmune or simultaneous disease. The secondary colorectal cancer cases were also excluded. The controls were unrelated healthy volunteers without history of autoimmune or any other disease referred to the hospital for routine consultations or fast track problems. The ethnicity of all participants was Lur. The purity of ethnicities was evaluated through their 2 previous generations.