Dataset Information

Tumor necrosis factor-? induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study.

ABSTRACT: BACKGROUND: 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. METHOD: 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). RESULTS: 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. CONCLUSIONS: 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3362607 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-α induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study.

Zhang Yan Y Wang Meng-Yun MY He Jing J Wang Jiu-Cun JC Yang Ya-Jun YJ Jin Li L Chen Zhi-Yu ZY Ma Xue-Jun XJ Sun Meng-Hong MH Xia Kai-Qin KQ Hong Xiao-Nan XN Wei Qing-Yi QY Zhou Xiao-Yan XY

PloS one 20120529 5

<h4>Background</h4>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.<h4>Method</h4>We used the Taqman assay to genotype six pote ...[more]

PMID: 22666399

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Project description:Non-Hodgkin's lymphoma (NHL) is a cancer closely associated with immune function, and the tumor necrosis factor (TNF) G-308A promoter polymorphism, which influences immune function and regulation, was recently reported by the InterLymph Consortium to be associated with NHL risk. TNF signaling activates the nuclear factor-kappaB (NF-kappaB) canonical pathway, leading to transcriptional activation of multiple genes that influence inflammation and immune response. We hypothesized that, in addition to TNF signaling, common genetic variation in genes from the NF-kappaB canonical pathway may affect risk of NHL. We genotyped 54 single nucleotide polymorphisms (SNP) within TNF, lymphotoxin A LTA, and nine NF-kappaB genes from the canonical pathway (TNFRSF1A, TRADD, TRAF2, TRAF5, RIPK1, CHUK, IKBKB, NFKB1, and REL) in a clinic-based study of 441 incident cases and 475 frequency-matched controls. Tagging SNPs were selected from HapMap supplemented by putative functional SNPs for LTA/TNF. We used principal components and haplo.stats to model gene-level associations and logistic regression to model SNP-level associations. Compared with the wild-type (GG), the AA genotype for the TNF promoter polymorphism G-308A (rs1800629) was associated with increased risk of NHL [odds ratio (OR), 2.14; 95% confidence interval (95% CI), 0.94-4.85], whereas the GA genotype was not (OR, 1.00; 95% CI, 0.74-1.34). This association was similar for follicular lymphoma and diffuse large B-cell lymphoma. A previously reported LTA/TNF haplotype was also associated with NHL risk. In gene-level analysis of the NF-kappaB pathway, only NFKB1 showed a statistically significant association with NHL (P = 0.049), and one NFKB1 tagSNP (rs4648022) was associated with NHL risk overall (ordinal OR, 0.59; 95% CI, 0.41-0.84; Ptrend = 0.0037) and for each of the common subtypes. In conclusion, we provide additional evidence for the role of genetic variation in TNF and LTA SNPs and haplotypes with risk of NHL and also provide some of the first preliminary evidence for an association of genetic variation in NFKB1, a downstream target of TNF signaling, with risk of NHL.

Project description:BACKGROUND:Inflammation constitutes one of the important components of colorectal cancer (CRC) pathogenesis. Tumor necrosis factor-? (TNF-?), a cytokine and an important inflammatory mediator plays a pivotal role in the malignant cellular proliferation, angiogenesis, tissue invasion and metastasis in CRC. The studies on association of various polymorphisms in human TNF-? gene including TNF-?-308G/A single nucleotide polymorphism (SNP) are limited, mixed and inconclusive. MATERIALS AND METHODS:The aim of this study was to analyze the association of TNF-?-308G/A promoter SNP with colorectal cancer (CRC) susceptibility and development risk and also to evaluate the modifying effects of possible TNF-?-308G/A genotypes on different risk factors of CRC in ethnic population of Kashmir, India through a case-control setup. The genotype frequencies of TNF-?-308G/A promoter SNP were compared between 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The associations between the TNF-?-308G/A SNP and CRC risk were examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. Further, the associations between this SNP and various clinico-pathological parameters, demographic variables and environmental factors within the case group subjects with regard to CRC risk were also evaluated. RESULTS:The association between the TNF-?-308G/A SNP and the modulation of risk of CRC was not found to be significant (p value = 0.156). The effect of less common TNF-?-308A allele on the risk of colorectal cancer was also not found to be significant (p value = 0.175). The variant genotype (AA) was nonexistent in the study population. Further, we found no significant effect modulation of CRC risk by wild and heterozygous TNF-?-308G/A SNP genotypes in presence of different possible risk factors (p > 0.05). We also found no significant association of TNF-?-308G/A SNP with the subsets of various characteristics of the case group subjects under study (p > 0.05). CONCLUSIONS:This study indicates that there is no significant association between the TNF-?-308G/A promoter SNP and the risk of developing CRC in ethnic Kashmiri population. However, in order to substantiate our findings, this study needs to be replicated with bigger sample size and should involve other ethnically defined populations with high CRC risk.

Project description:OBJECTIVE:Several published studies have investigated the association between the -308G/A (rs1800629) polymorphism in the tumor necrosis factor-? (TNF-?) gene and the risk of dilated cardiomyopathy (DCM). However, the TNF-? gene polymorphism has a controversial role in the pathogenesis of DCM among different populations. In the present study, a meta-analysis was performed to resolve this inconsistency. METHODS:Potentially eligible papers reporting an association between the TNF-? rs1800629 polymorphism and DCM susceptibility were searched in 4 databases including PubMed, EMBASE, Chinese Biomedical Database (CBM), and the Cochrane Library up to April 1, 2018. The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Subgroup analysis based on the ethnicity, studies with or without ischemic and valvular DCM was conducted. Publication bias detection was conducted using Begg test. RESULTS:Nine papers detailing case-control studies were included, reporting a total of 1339 DCM cases and 1677 healthy controls. The meta-analysis results indicated that TNF-? rs1800629 was associated with increased DCM susceptibility in the populations studied under the heterozygous model (AG vs GG: OR?=?1.91, 95% CI?=?1.05-3.50, P?=?.035) and dominant model (AG?+?AA vs GG: OR?=?1.87, 95% CI?=?1.01-3.45, P?=?.046). In the subgroup analysis for ethnicity, rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians under the 5 models (A vs G: OR?=?2.87, 95% CI?=?1.56-5.30, P?=?.001; AA vs GG: OR?=?3.95, 95% CI?=?1.13-13.82, P?=?0.031; AG vs GG: OR?=?3.8, 95% CI?=?1.57-9.19, P?=?.003; AA vs GG?+?AG: OR?=?2.51, 95% CI?=?1.41-4.49, P?=?.002; AG?+?AA vs GG: OR?=?3.77, 95% CI?=?1.54-9.20, P?=?.004). CONCLUSION:There may be a moderate association between TNF-? rs1800629 polymorphism and DCM susceptibility in the whole populations studied; however, TNF-? rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians, which indicates that such associations may be different between ethnicities.

Dataset Information

Tumor necrosis factor-? induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study.

Publications

Tumor necrosis factor-α induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study.

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