Interleukin 10 gene −1082A/G polymorphism is associated with osteosarcoma risk and poor outcomes in the Chinese population

Interleukin-10 (IL-10) is a multifunctional cytokine that participates in the development and progression of various malignant tumors. However, data regarding the role of IL-10 polymorphisms in osteosarcoma development are not available. A case–control study was conducted in 260 patients with osteosarcoma and 260 healthy controls to investigate the possible association between IL-10 polymorphisms and the risk of osteosarcoma. Our results indicate the IL-10 −1082A/G (rs1800896) polymorphism is significantly associated with an increased risk of osteosarcoma in all genetic models (AG vs. AA, odds ratio (OR) = 1.56; 95 % confidence interval (CI) = 1.28–2.32, P = 0.017; GG vs. AA, OR = 1.62, 95 % CI 1.24–2.61, P = 0.013; AG + GG vs. CC, OR = 1.76, 95 % CI = 1.31–3.01, P = 0.019). However, the genotype and allele frequencies of IL-10 −819C/T (rs1800871) and −592A/C (rs1800872) polymorphisms in osteosarcoma patients did not significantly differ from controls. Further analyses revealed that the IL-10 −1082A/G (rs1800896) genotypes were associated with advanced tumor stages and metastasis in osteosarcoma patients. Additionally, a statistically significant association between the IL-10 −1082A/G (rs1800896) genotype and poor survival in osteosarcoma patients was observed. Our results demonstrate that the IL-10 −1082A/G (rs1800896) genotype is associated with an increased susceptibility and worse outcome for osteosarcoma patients in the Chinese Han population.

[1]  M. Nielen,et al.  Prognostic factors in canine appendicular osteosarcoma – a meta-analysis , 2012, BMC Veterinary Research.

[2]  K. Xie,et al.  Interleukin-8 and human cancer biology. , 2001, Cytokine & growth factor reviews.

[3]  R. Coffman,et al.  Interleukin-10 and the interleukin-10 receptor. , 2001, Annual review of immunology.

[4]  R. Westendorp,et al.  Novel Single Nucleotide Polymorphisms in the Distal IL-10 Promoter Affect IL-10 Production and Enhance the Risk of Systemic Lupus Erythematosus1 , 2001, The Journal of Immunology.

[5]  F. Marincola,et al.  Interleukin‐10 and the immune response against cancer: a counterpoint , 2005, Journal of leukocyte biology.

[6]  H. Sugimura,et al.  Effects of interleukin‐10 gene polymorphism on the development of gastric cancer and peptic ulcer in Japanese subjects , 2007, Journal of gastroenterology and hepatology.

[7]  J. Li,et al.  Predictive role of Glutathione S-transferases (GSTs) on the prognosis of osteosarcoma patients treated with chemotherapy , 2013, Pakistan journal of medical sciences.

[8]  K. Asadullah,et al.  Interleukin-10 Therapy—Review of a New Approach , 2003, Pharmacological Reviews.

[9]  R. Eeles,et al.  Influence of cytokine gene polymorphisms on the development of prostate cancer. , 2002, Cancer research.

[10]  Stefano Landi,et al.  Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. , 2003, Cancer research.

[11]  R. Gorlick,et al.  Chemotherapy resistance in osteosarcoma: current challenges and future directions , 2006, Expert review of anticancer therapy.

[12]  M. Lazarus,et al.  An investigation of polymorphism in the interleukin-10 gene promoter. , 1997, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[13]  Y. Bao,et al.  Predictive impact of common variations in DNA repair genes on clinical outcome of osteosarcoma. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[14]  F. Marincola,et al.  The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle. , 2004, Cytokine & growth factor reviews.

[15]  E. Vairaktaris,et al.  The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma. , 2007, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[16]  H. Granger,et al.  Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10. , 2000, Blood.

[17]  M. Gebhardt,et al.  Biology and therapeutic advances for pediatric osteosarcoma. , 2004, The oncologist.

[18]  R. de Waal Malefyt,et al.  Functional characterization of human IL-10. , 1992, International archives of allergy and immunology.

[19]  E. Kramárová,et al.  The international classification of childhood cancer , 1996, International journal of cancer.

[20]  Kevin B. Jones,et al.  miRNA signatures associate with pathogenesis and progression of osteosarcoma. , 2012, Cancer research.