title: 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.
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Ningbo Medical Center, Lihuili Hospital, Ningbo, Zhejiang, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Bank of Blood Products, Ningbo No.2 Hospital, Ningbo, Zhejiang, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Jingmi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Xianru
authors.initials: X
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo, Zhejiang, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias; D012306:Risk
chemical_list: D008233:Lymphotoxin-alpha