title: Potentially functional polymorphisms in PAK1 are associated with risk of lung cancer in a Chinese population.
abstract: P21-activated kinase 1(PAK1) plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis and has been implicated with tumorigenesis and tumor progression. We hypothesized that functional polymorphisms in PAK1 gene may modify the risk of lung cancer. We screened four potentially functional polymorphisms (rs2154754, rs3015993, rs7109645, and rs2844337) in PAK1 gene and evaluated the association between the genetic variants and lung cancer risk in a case-control study including 1341 lung cancer cases and 1982 cancer-free controls in a Chinese population. We found that variant allele of rs2154754 was significantly associated with a decreased risk of lung cancer (OR = 0.85, 95% CI: 0.77-0.95, P = 0.004), meanwhile the result of rs3015993 was marginal (OR = 0.90, 95%CI: 0.81-1.00, P = 0.044). After multiple comparisons, rs2154754 was still significantly associated with the lung cancer risk (P < 0.0125 for Bonferroni correction). We also detected a significant interaction between rs2154754 genotypes and smoking levels on lung cancer risk (P = 0.042). Combined analysis of these two polymorphisms showed a significant allele-dosage association between the number of protective alleles and reduced risk of lung cancer (Ptrend = 0.008). These findings indicate that genetic variants in PAK1 gene may contribute to susceptibility to lung cancer in the Chinese population.
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214043, China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210009, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Cardiothoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214043, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012307:Risk Factors; D054462:p21-Activated Kinases / Q000235:genetics*
chemical_list: C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: Interaction; PAK1; lung cancer; polymorphisms; susceptibility