Quantitative assessment of the influence of TP63 gene polymorphisms and lung cancer risk: evidence based on 93,751 subjects.
BACKGROUND
Several genome-wide association studies on lung cancer (LC) have reported similar findings of a new susceptibility locus, 3q28. After that, a number of studies reported that the rs10937405, and rs4488809 polymorphism in chromosome 3q28 has been implicated in LC risk. However, the studies have yielded contradictory results.


METHODS
PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between rs10937405, rs4488809 polymorphism at 3q28 and susceptibility to LC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested.


RESULTS
A total of 9 studies including 35,961 LC cases and 57,790 controls were involved in this meta-analysis. An overall random-effects per-allele OR of1.19 (95% CI: 1.14-1.25; P<10(-5)) and 1.19 (95% CI: 1.13-1.25; P<10(-5)) was found for the rs10937405 and rs4488809 polymorphism respectively. Similar results were also observed using dominant or recessive genetic model. After stratified by ethnicity, significant associations were found among East Asians (per-allele OR = 1.22, 95% CI: 1.17-1.27; P<10(-5)); whereas no significant associations were found among Caucasians for rs10937405. In the sub-group analysis by sample size, significantly increased risks were found for these polymorphisms in all genetic models. When analyzed according to histological type, the effects of rs10937405, and rs4488809 at 3q28 on the risk of lung cancer were significant mostly for lung adenocarcinoma.


CONCLUSIONS
Our findings demonstrated that rs10937405-G allele and rs4488809-G allele might be risk-conferring factors for the development of lung cancer, especially for East Asian populations.
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Liang
L
Zhang
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Xiao-Feng
XF
Wang
Department of Nuclear Medicine, Shanghai 10th People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Yu-Shui
YS
Ma
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Qing
Q
Xia
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Feng
F
Zhang
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China ; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Da
D
Fu
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Yi-Chao
YC
Wang
D000230:Adenocarcinoma / Q000209:etiology*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins