Abstract
BackgroundThe association between polymorphisms on 15q25.1 and lung cancer has been widely evaluated; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two polymorphisms (CHRNA3 gene: rs1051730 and AGPHD1 gene: rs8034191) on 15q25.1.MethodsData were extracted from 15 and 14 studies on polymorphisms rs1051730 and rs8034191 involving 12301/14000 and 14075/12873 lung cancer cases/controls, respectively. The random-effects model was applied, addressing heterogeneity and publication bias.ResultsThe two polymorphisms followed Hardy-Weinberg equilibrium for all studies (P>0.05). For rs1051730-G/A, carriers of A allele had a 36% increased risk for lung cancer (95% confidence interval [CI]: 1.27–1.46; P<0.0005), without heterogeneity (P = 0.258) or publication bias (PEgger = 0.462). For rs8034191-T/C, the allelic contrast indicated that C allele conferred a 23% increased risk for lung cancer (95% CI: 1.08–1.4; P = 0.002), with significant heterogeneity (P<0.0005), without publication bias (PEgger = 0.682). Subgroup analyses suggested that the between-study heterogeneity was derived from ethnicity, study design, matched information, and lung cancer subtypes. For example, the association of polymorphisms rs1051730 and rs8034191 with lung cancer was heterogeneous between Caucasians (OR = 1.32 and 1.22; 95% CI: 1.25–1.44 and 1.05–1.42; P<0.0005 and 0.008, respectively) and East Asians (OR = 1.51 and 1.03; 95% CI: 0.76–3 and 0.47–2.27; P = 0.237 and 0.934, respectively) under the allelic model, and this association was relatively strengthened under the dominant model. There was no observable publication bias for both polymorphisms.ConclusionsOur findings demonstrated that CHRNA3 gene rs1051730-A allele and AGPHD1 gene rs8034191-T allele might be risk-conferring factors for the development of lung cancer in Caucasians, but not in East-Asians.
Highlights
Lung cancer is the most common malignancy and the firstleading cause of cancer mortality, with an estimated 1.3 million new cases diagnosed annually in the world [1,2]
To derive a more precise estimation and investigate the inconsistency, we evaluated the effect of two polymorphisms rs1051730 and rs8034191 on the risk of lung cancer, addressing heterogeneity and publication bias
40 potentially relevant articles, of which 12 met the inclusion criteria in an attempt to evaluate the association of CHRNA3 gene rs1051730 and/or AGPHD1 gene rs8034191 polymorphisms with lung cancer risk [5,16,17,18,19,20,21,22,23,24,25,26]
Summary
Lung cancer is the most common malignancy and the firstleading cause of cancer mortality, with an estimated 1.3 million new cases diagnosed annually in the world [1,2]. The chromosome 15q25.1 region has been identified as a hotspot for lung cancer susceptibility by recent genome-wide association (GWA) studies [5,6,7,8]. Results of genetic association studies for nicotine dependence, smoking behavior, and smokingrelated diseases have converged to implicate the chromosome 15q25.1 region. The relationship between polymorphisms rs1051730 in CHRNA3 gene and rs8034191 in the AGPHD1 gene and lung cancer risk or related phenotypes has been widely investigated. To derive a more precise estimation and investigate the inconsistency, we evaluated the effect of two polymorphisms rs1051730 and rs8034191 on the risk of lung cancer, addressing heterogeneity and publication bias. The association between polymorphisms on 15q25.1 and lung cancer has been widely evaluated; the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two polymorphisms (CHRNA3 gene: rs1051730 and AGPHD1 gene: rs8034191) on 15q25.1
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