The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01–1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01–1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.
References
[1]
Jiang L, Zhou P, Sun A, Zheng J, Liu B, et al. (2011) Functional variant (？1304T>G) in the MKK4 promoter is associated with decreased risk of acute myeloid leukemia in a southern Chinese population. Cancer Sci 102: 1462–1468.
[2]
Le Beau MM, Albain KS, Larson RA, Vardiman JW, Davis EM, et al. (1986) Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol 4: 325–345.
[3]
Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, et al. (1993) Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 329: 909–914.
[4]
Gunz FW, Veale AM (1969) Leukemia in close relatives–accident or predisposition? J Natl Cancer Inst 42: 517–524.
[5]
Evans DI, Steward JK (1972) Down’s syndrome and leukaemia. Lancet 2: 1322.
[6]
Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, et al. (2007) Interleukin-12: biological properties and clinical application. Clin Cancer Res 13: 4677–4685.
[7]
Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3: 133–146.
[8]
Hunter CA (2005) New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol 5: 521–531.
[9]
Cocco C, Morandi F, Airoldi I (2011) Interleukin-27 and interleukin-23 modulate human plasmacell functions. J Leukoc Biol 89: 729–734.
[10]
Cocco C, Canale S, Frasson C, Di Carlo E, Ognio E, et al. (2010) Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells. Blood 116: 3887–3898.
[11]
Parham C, Chirica M, Timans J, Vaisberg E, Travis M, et al. (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168: 5699–5708.
[12]
Xu Y, Liu Y, Pan S, Liu L, Liu J, et al.. (2012) IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population. J Gastroenterol. [Epub ahead of print].
[13]
Chu H, Cao W, Chen W, Pan S, Xiao Y, et al. (2012) Potentially functional polymorphisms in IL-23 receptor and risk of esophageal cancer in a Chinese population. Int J Cancer 130: 1093–1097.
[14]
Chen J, Lu Y, Zhang H, Ding Y, Ren C, et al. (2010) A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population. Mol Carcinog 49: 862–868.
[15]
Ferretti E, Di Carlo E, Cocco C, Ribatti D, Sorrentino C, et al. (2010) Direct inhibition of human acute myeloid leukemia cell growth by IL-12. Immunol Lett 133: 99–105.
[16]
Langowski JL, Kastelein RA, Oft M (2007) Swords into plowshares: IL-23 repurposes tumor immune surveillance. Trends Immunol 28: 207–212.
Tartour E, Fossiez F, Joyeux I, Galinha A, Gey A, et al. (1999) Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res 59: 3698–3704.
[19]
Oniki S, Nagai H, Horikawa T, Furukawa J, Belladonna ML, et al. (2006) Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res 66: 6395–6404.
[20]
Ugai S, Shimozato O, Yu L, Wang YQ, Kawamura K, et al. (2003) Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects. Cancer Gene Ther 10: 771–778.
[21]
Yuan X, Hu J, Belladonna ML, Black KL, Yu JS (2006) Interleukin-23-expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma. Cancer Res 66: 2630–2638.
[22]
Hu J, Yuan X, Belladonna ML, Ong JM, Wachsmann-Hogiu S, et al. (2006) Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Cancer Res 66: 8887–8896.
[23]
Kaiga T, Sato M, Kaneda H, Iwakura Y, Takayama T, et al. (2007) Systemic administration of IL-23 induces potent antitumor immunity primarily mediated through Th1-type response in association with the endogenously expressed IL-12. J Immunol 178: 7571–7580.
[24]
Overwijk WW, de Visser KE, Tirion FH, de Jong LA, Pols TW, et al. (2006) Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant. J Immunol 176: 5213–5222.
[25]
Kim ES, Kim SW, Moon CM, Park JJ, Kim TI, Kim WH, Cheon JH. Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet’s disease in Korean population. Life Sci. 2012 May 22;90(19–20): 740–6. Epub 2012 Mar 27.
[26]
Faragó B, Magyari L, Sáfrány E, Cs？ngei V, Járomi L, Horvatovich K, Sipeky C, Maász A, Radics J, Gyetvai A, Szekanecz Z, Czirják L, Melegh B. Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis. 2008 Feb;67(2): 248–50. Epub 2007 Jul 2.
[27]
Safrany E, Szabo M, Szell M, Kemeny L, Sumegi K, Melegh BI, Magyari L, Matyas P, Figler M, Weber A, Tulassay Z, Melegh B. Difference of interleukin-23 receptor gene haplotype variants in ulcerative colitis compared to Crohn’s disease and psoriasis. Inflamm Res. 2012 Oct 25. [Epub ahead of print].
[28]
Kan SH, Mancini G, Gallagher G (2008) Identification and characterization of multiple splice forms of the human interleukin-23 receptor alpha chain in mitogen-activated leukocytes. Genes Immun 9: 631–639.
[29]
Conde L, Vaquerizas JM, Dopazo H, Arbiza L, Reumers J, et al. (2006) PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes. Nucleic Acids Res 34: W621–625.
[30]
Bossard P, Zaret KS (1998) GATA transcription factors as potentiators of gut endoderm differentiation. Development 125: 4909–4917.
[31]
Chou J, Provot S, Werb Z (2010) GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 222: 42–49.
