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

Abstract

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.

Associations between inflammatory gene polymorphisms (TNF-α 308G/A, TNF-α 238G/A, TNF-β 252A/G, TGF-β1 29T/C, IL-6 174G/C and IL-10 1082A/G) and susceptibility to osteosarcoma: a meta-analysis and literature review

“…A total of nine studies [ 26 , 29 , 32 , 33 , 36 – 40 ] with 1119 cases and 1358 controls were recruited in this meta-analysis. The process of study selection and the inclusion process are shown in Figure 1 .…”

“…Ma et al [ 38 ], Xu et al [ 39 ] and Wu et al [ 40 ] reported the alleles and genotypes of TGF-β1 29T/C polymorphism. Oliveira et al [ 26 ] reported the alleles and genotypes of IL-6 174G/C and IL-10 1082A/G polymorphism, and these two polymorphisms were also studied by Qi et al [ 32 ] and Cui et al [ 33 ]. Furthermore, seven studies [ 29 , 32 , 33 , 37 – 40 ] were performed in Asian populations, and the other two studies [ 26 , 36 ] were conducted in Caucasian populations.…”

“…Multiple factors are involved in the etiology of OS, among which genetics and gene polymorphisms have aroused increased attention [ 1 , 4 , 8 ]. Given the important roles of inflammation and gene polymorphisms in cancer etiology and progression, more studies have been performed to explore the associations between inflammatory gene polymorphisms and susceptibility to OS [ 26 , 29 , 32 , 33 , 36 – 40 , 48 , 49 ]. Although several studies including Patio-Garcia et al [ 36 ], Oliveira et al [ 26 ], Zhao et al [ 29 ] and Xie et al [ 37 ] have explored the possible association between TNF-α 308G/A polymorphism and OS risk, there results are inconsistent.…”

Association of three promoter polymorphisms in interleukin-10 gene with cancer susceptibility in the Chinese population: a meta-analysis

“…Ultimately, 53 articles were included in the final meta-analysis. Of these 53 articles, 24 articles [ 40 – 63 ] include 26 studies examining IL-10 -1082A/G polymorphism, 28 articles [ 18 , 42 , 43 , 45 , 47 , 49 , 52 , 53 , 57 - 61 , 63 - 77 ] include 33 studies examining the -819T/C polymorphism, and 39 articles [ 18 , 42 , 43 , 45 , 47 , 52 , 53 , 56 - 67 , 69 , 70 , 73 - 76 , 78 - 91 ] include 42 studies examining the -592A/C polymorphism (Table 1 ). Of the 53 articles, two publications [ 18 , 45 ] with three cancer types were considered as three studies and one publication [ 65 ] with two cancer types were also considered as two studies.…”

“…For the studies assessing three polymorphisms (-1082A/G, -819T/C and -592A/C) [ 32 , 37 ], two (-1082A/G and -592A/C) [ 31 ], only one such as -1082A/G [ 29 , 30 , 33 - 35 , 38 ] or -819T/C [ 36 , 39 ] polymorphism and cancer risk but no other IL-10 gene polymorphisms, the genotypes distribution in the controls were deviated from HWE, thus, these studies were excluded in the final analysis. Sixteen studies were also deviated from HWE, but the genotypes distribution in the controls of eight studies [ 18 , 64 - 67 , 70 , 73 , 76 ] were consistent with that expected from the HWE for both -819T/C and -592A/C polymorphisms, five [ 81 , 84 , 86 , 87 , 90 ] for the -592A/C polymorphism and three [ 41 , 48 , 54 ] for the -1082A/G polymorphism, thus, these studies were included in the final analysis. For those studies [ 18 , 45 , 65 ] with the same control subjects, the control numbers were calculated once in the total number.…”