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, I2 = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I2 = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I2 = 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, I2 = 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, I2 = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I2 = 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.
Highlights
With the high prevalence and mortality rate, cancers have become one of the main causes of morbidity and mortality worldwide [1]
Inclusion criteria Articles enrolled in our meta-analyses met the following inclusion criteria: (1) evaluating the association between LTA polymorphism rs1041981, rs2239704, rs2229094 or rs746868 and cancer risk; (2) case-control study; (3) results with sufficient published data to estimate an OR with a 95% CI; (4) the genotype distribution in controls met Hardy-Weinberg equilibrium (HWE)
After reading the title or abstract, 50 studies concerning the association for the four LTA polymorphisms and cancer risk were considered for the following step
Summary
With the high prevalence and mortality rate, cancers have become one of the main causes of morbidity and mortality worldwide [1]. Large epidemiologic and clinical studies have illustrated that inflammation may be associated with the development of cancers [3,4]. Increasing evidence suggests that predisposition to cancer is associated with cytokines [5,6], such as tumor necrosis factors (TNF) [7,8]. Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine belong to the TNF family which plays an important role in the inflammatory and immunologic response [9]. LTA gene is located on the 6p21.3 that harbors the class III region of the major histocompatibility complex (MHC) locus [13]. Genetic variations of inflammation-related genes are shown to alter both the regulation of the inflammatory response and modulation of susceptibility to radiation-induced normal tissue damage [14]
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