Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

Abstract

BackgroundInflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk.MethodsA case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area.ResultsDiagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms.ConclusionOur results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.

The Unexpected Pleiotropic Activities of RANTES

“…However, RANTES can have detrimental effects via the recruitment of immune cells that enhance inflammatory processes such as arthritis, atopic dermatitis, nephritis, colitis, and other disorders (e.g., arteriosclerosis, pulmonary hypertension, asthma, nasal polyps, endometriosis, nephropathy, and perhaps Alzheimer's disease) (1,3). This cytokine has been associated as well with the induction or promotion of cancer (e.g., prostate and breast) (3,5,6). In this latter situation, RANTES can be angiogenic and also increase the metastatic potential of cancer cells by encouraging cellular migration to sites of its production (3).…”

Genetic Polymorphism of Interleukin-1A (IL-1A), IL-1B, and IL-1 Receptor Antagonist (IL-1RN) and Prostate Cancer Risk

“…The other article was exclude since it mainly discussed IL-1B and fatigue in PCa patients treated with androgen deprivation therapy (Jim et al, 2012). Thus, a total of 9 records with 141 studies excluded a7er ,tle and abstract review for one of the reasons: --87 records were not related gene polymorphism --43 records were polymorphism other than IL--1 family (IL--1A, IL--1B, and IL--1RN) --11 records were reviews or meta--analysis 0 studies iden,fied through checking reference lists of other papers 12 studies for further scanning 3 studies excluded for one of the reasons: --1 concerning prostate cancer aggressiveness --1 concerning prostate cancer recurrence --1 concerning fa,gue in prostate cancer pa,ents treated with androgen depriva,on therapy Genetic Polymorphism of , and Prostate Cancer Risk a case-control design met the inclusion criteria for the meta-analysis, including 1 study for IL-1A (Saenz-Lopez et al, 2008), 5 studies for IL-1B (McCarron et al, 2002;Michaud et al, 2006;Zabaleta et al, 2008;Wang et al, 2009;Zhang et al, 2010), and 3 studies for IL-1RN (Lindmark et al, 2005;Xu et al, 2005;Cheng et al, 2007).…”

“…Among them, 5 were performed in Caucasians populations, and the other 4 were performed in mixed populations. Only 1 study (Saenz-Lopez et al, 2008) discussed IL-1A-889 (rs1800587) polymorphism and PCa risk. 5 studies investigated IL-1B polymorphism and PCa risk, of which 4 studies (McCarron et al, 2002;Michaud et al, 2006;Zabaleta et al, 2008;Zhang et al, 2010) examined IL-1B-511 (rs16944) polymorphism, 2 studies (Michaud et al, 2006;Zabaleta et al, 2008) examined IL-1B+3953 (rs1143634) polymorphism, and 2 studies (Zabaleta et al, 2008;Wang et al, 2009) examined IL-1B-31 (rs1143627) polymorphism.…”

Association of tumor necrosis factor-α 308G/A polymorphism with urogenital cancer risk: a systematic review and meta-analysis

“…There are 13 studies (Oh et al, 2000;McCarron et al, 2002;Wu, 2004;Jinchao, 2007;Danforth et al, 2008;Sáenz-López et al, 2008;Zabaleta et al, 2008;Kesarwani, 2009;Moore et al, 2009;Wang et al, 2009a;Zhang et al, 2010;Berhane et al, 2012;Jones et al, 2013) focusing on prostate cancer, 19 studies (Jang et al, 2001;Calhoun et al, 2002;Gostout et al, 2003;Stanczuk et al, 2003;Deshpande et al, 2005;Duarte et al, 2005;Govan, 2006;Kohaar et al, 2007;Singh, 2009;Wang et al, 2009b;Ivansson, 2010;Zu, 2010;Wang et al, 2011;Zuo et al, 2011;Badano et al, 2012;Barbisan et al, 2012;Hang and Xu, 2012;Wang et al, 2012;Sousa et al, 2014) on cervical cancer, 6 studies (Tsai et al, 2001;Jeong et al, 2004;Kim et al, 2005;Leibovici et al, 2005;Nonomura et al, 2006;Ahirwar et al, 2008) on bladder cancer, 1 study (Jang et al, 2001) on renal cell cancer, and 1 study (Wu, 2013) on urothelial carcinoma. Five articles (Stanczuk et al, 2003;…”