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Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis.

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.

SUBMITTER: Huang Y

PROVIDER: S-EPMC3861395 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis.

Huang Yi Y Yu Xi X Wang Lingyan L Zhou Shengjun S Sun Jie J Feng Nan N Nie Sheng S Wu Jingmi J Gao Feng F Fei Bing B Wang Jianyong J Lin Zhiqing Z Li Xianru X Xu Leiting L Gao Xiang X Ye Meng M Duan Shiwei S

PloS one 20131212 12

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-an ...[more]

PMID: 24349304

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Project description:BackgroundThe associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but the results remain controversial. To investigate whether these polymorphisms facilitate susceptibility to PCOS, we conducted a comprehensive systematic review and meta-analysis.MethodsPubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to obtain the genetic association studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95 % confidence intervals (CI) were used to assess the strengths of the associations. Funnel plots and Egger's tests were performed to test for possible publication bias. All statistical analyses were performed using Review Manager 5.2 and STATA11.0.ResultsEighteen articles were included in the final meta-analysis. The studies involved the following polymorphisms: TNF-α -308G > A, TNF-α -805C>T, TNF-α -1031 T>C, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953 T>C, IL-6 -174G>C, IL-10 -819C>T, IL-10 -1082A>G, IL-18 -607C>A, and IL-18 -137G>C. Our results show a significant association between PCOS risk and the TNF-α -1031 T>C polymorphism (For TC+CC vs. TT: OR=2.09, 95 % CI=1.58-2.76, p<0.0001. For C allele vs. T allele: OR=1.67, 95 % CI=1.33-2.09, p<0.0001) and between PCOS risk and the IL-6 -174>C polymorphism (For CC+GC vs. GG: OR=0.49, 95 % CI=0.25-0.95, p=0.03. For CC vs. GG: OR=0.48, 95 % CI=0.28-0.80, p=0.005. For C vs. G: OR=0.60, 95 % CI=0.42-0.87, p=0.007). No associations were found with the other genetic models.ConclusionThe results of the meta-analysis suggest positive associations between the TNF-α -1031 T>C and IL-6 -174G>C polymorphisms and the risk of PCOS. No associations are found between PCOS risk and the TNF-α -308G>A, TNF-α -805C>T, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953C>T, IL-10 -819C>T, IL-10 -1082 A>G, IL-18 -607C>A, and IL-18 -137G>C polymorphisms. However, due to the heterogeneity and low quality of the studies related to PCOS polymorphisms in the meta-analysis, the results should be interpreted with caution. Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed.

Dataset Information

Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis.

Publications

Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis.

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