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Biosci Rep. 2019 Jan 15;39(1). pii: BSR20181052. doi: 10.1042/BSR20181052. Print 2019 Jan 31.

A trial sequential meta-analysis of TNF-α -308G>A (rs800629) gene polymorphism and susceptibility to colorectal cancer.

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Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142, Saudi Arabia.
Department of Life and Environmental Sciences, College of Natural and Health Sciences, Zayed University, P.O. Box 19282, Dubai, United Arab Emirates.
School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai, United Arab Emirates.
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha 65431, Saudi Arabia.
Centre for Life Sciences, Central University of Jharkhand, Ranchi 835205, Jharkhand, India.
Department of Emergency Medical Services, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia.
Department of Biotechnology, Institute of Engineering and Technology, Lucknow 226021, Uttar Pradesh, India.
Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142, Saudi Arabia



Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-308 G>A gene polymorphism with CRC risk.


Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association.


The pooled analysis indicated no risk associated with TNF-308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863-1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688-2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843-1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849-1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686-2.033). Subgroup analysis revealed that TNF-308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias.


No association of TNF-308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α -308 G>A SNP in the etiology of CRC and to endorse the present findings.


Colorectal cancer; Meta-analysis; Tumor Necrosis Factor-α; polymorphism; susceptibility

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