Article

Tumor Necrosis Factor-α Induced Protein 8 Polymorphism and Risk of Non-Hodgkin’s Lymphoma in a Chinese Population: A Case-Control Study

University of Navarra, Center for Applied Medical Research, Spain
PLoS ONE (Impact Factor: 3.23). 05/2012; 7(5):e37846. DOI: 10.1371/journal.pone.0037846
Source: PubMed

ABSTRACT

Non-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population.
We used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI).
We observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49-3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41-2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes.
The polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

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Available from: Jing He, Jan 10, 2014
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    • "The association is significant between LTA polymorphisms and cancers including gastric [15] and breast [17] cancers in Asians, colorectal cancer [18] in Germans, and Non-Hodgkin Lymphoma (NHL) in Europeans [19-21]. However, discrepancies remain for the association of LTA polymorphisms with cancers in different ethnic groups [15,16,22-24]. "
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    ABSTRACT: Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the inflammatory and immunologic response. Numerous studies have shown LTA polymorphisms as risk factors for cancers, but the results remain inconclusive. The goal of the present meta-analyses is to establish the associations between cancers and four LTA variants (rs1041981, rs2239704, rs2229094 and rs746868). A total of 30 case-control studies involving 58,649 participants were included in the current meta-analyses. Our results showed significant associations with increased cancer risk for rs1041981 (odd ratio (OR) = 1.15, 99% confidential interval (CI) = 1.07-1.25, P < 0.0001, I(2) = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I(2) = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I(2) = 0.0%). No evidence was found for the association between rs746868 and cancer risk (OR = 1.01, 99% CI = 0.93-1.10, P = 0.771, I(2) = 0.0%). Subgroup meta-analysis suggested that rs2239704 was likely to increase the risk of hematological malignancy (OR = 1.10, 99% CI = 1.01-1.20, P = 0.023, I(2) = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I(2) = 0.0%). In conclusion, our meta-analyses suggested that the LTA rs1041981, rs2239704 and rs2229094 polymorphisms contributed to the increased risk of cancers. Future functional studies were needed to clarify the mechanistic roles of the three variants in the cancer risk.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "We have studied the association between inflammation and immune-related gene polymorphisms and risk of NHL previously [11]. We genotyped six SNPs (TNF rs1799964T>C, LTA rs1800683G>A, IL–10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) and found that one SNP (rs1045241) in TNFAIP8 contributed to NHL susceptibility in a Chinese population. "
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    ABSTRACT: Non-Hodgkin's lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population. We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors. We observed that LTA rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06-2.51; P = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10-2.04, P = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and LTA rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated β2-MG level before treatment indicated poorer prognosis. The polymorphism of LTA rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.
    Preview · Article · Jun 2013 · PLoS ONE
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    ABSTRACT: TNFAIP8 is an anti-apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA binding sites may change mRNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted OR=2.16, 95% CI=1.16-4.03, P=0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to TNFAIP8 3'-UTR in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistances to cisplatin and nedaplatin and recurrence and death from cervical cancer. Taken together, although lacked information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.
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