title: Sipa1 promoter polymorphism predicts risk and metastasis of lung cancer in Chinese.
abstract: Signal-induced proliferation associated gene 1 (Sipa1) is a signal transducer to activate the Ras-related proteins and modulate cell progression, differentiation, adhesion and cancer metastasis. In this study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in Sipa1 are associated with lung cancer risk and metastasis. Three common SNPs (rs931127A > G, rs2448490G > A, and rs3741379G > T) were genotyped in a discovery set of southern Chinese population and then validated the promising SNPs in a validation set of an eastern Chinese population in a total of 1559 lung cancer patients and 1679 cancer-free controls. The results from the two sets were consistent, the rs931127GG variant genotype had an increased risk of lung cancer compared to the rs931127AA/GA genotypes (OR = 1.27; 95% CI = 1.09-1.49) after combination of the two populations, and the rs931127GG interacted with pack-year smoked on increasing lung cancer risk (P = 0.037); this SNP also had an effect on patients' clinical stages (P = 0.012) that those patients with the rs931127GG genotype had a significant higher metastasis rate and been advanced N, M stages at diagnosis. However, these associations were not observed for rs2448490G > A and rs3741379G > T in the discovery set. Our data suggest that the SNP rs931127A > G in the promoter of Sipa1 was significantly associated with lung cancer risk and metastasis, which may be a biomarker to predict the risk and metastasis of lung cancer.
authors: The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R., China; Dongguan Taiping People Hospital, Dongguan, P.R., China.
authors: Chenli
authors: C
authors: Xie
authors: Lei
authors: L
authors: Yang
authors: Xiaorong
authors: X
authors: Yang
authors: Rongrong
authors: R
authors: Yang
authors: Yinyan
authors: Y
authors: Li
authors: Fuman
authors: F
authors: Qiu
authors: Mei
authors: M
authors: Chen
authors: Wenxiang
authors: W
authors: Fang
authors: Xiaonong
authors: X
authors: Bin
authors: Jieqiong
authors: J
authors: Deng
authors: Dongsheng
authors: D
authors: Huang
authors: Bin
authors: B
authors: Liu
authors: Yifeng
authors: Y
authors: Zhou
authors: Jiachun
authors: J
authors: Lu
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000556:secondary; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000209:etiology / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000209:etiology* / Q000556:secondary; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human
keywords: lung cancer; metastasis; signal-induced proliferation associated gene 1; single nucleotide polymorphism