PURPOSE: Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample. PATIENTS AND METHODS: A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancer patients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls. RESULTS: Patients with genotypes GG or CG for the rs1862214 single nucleotide polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared with those with the common genotype CC showed an increased risk of lung cancer (odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship (HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. CONCLUSION: These results suggest that the rs1862214 polymorphism in PDCD5 is predictive for lung cancer risk and prognosis, and that PDCD5 may represent a novel tumor suppressor gene influencing lung cancer.
PURPOSE: Whole-genome scan association analysis was carried out to identify genetic variants predictive of lung cancer risk in smokers and to confirm the identified variants in an independent sample. PATIENTS AND METHODS: A case-control study was performed using two pools consisting of DNA from 322 German smoking lung cancerpatients and 273 healthy smoking controls, respectively. A replication study was carried out using 254 Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls. RESULTS:Patients with genotypes GG or CG for the rs1862214 single nucleotide polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared with those with the common genotype CC showed an increased risk of lung cancer (odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship (HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. HumanNCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. CONCLUSION: These results suggest that the rs1862214 polymorphism in PDCD5 is predictive for lung cancer risk and prognosis, and that PDCD5 may represent a novel tumor suppressor gene influencing lung cancer.
Authors: Juncheng Dai; Zhihua Li; Christopher I Amos; Rayjean J Hung; Adonina Tardon; Angeline S Andrew; Chu Chen; David C Christiani; Demetrios Albanes; Erik H F M van der Heijden; Eric J Duell; Gad Rennert; James D Mckay; Jian-Min Yuan; John K Field; Jonas Manjer; Kjell Grankvist; Loic Le Marchand; M Dawn Teare; Matthew B Schabath; Melinda C Aldrich; Ming-Sound Tsao; Philip Lazarus; Stephen Lam; Stig E Bojesen; Susanne Arnold; Xifeng Wu; Aage Haugen; Vladimir Janout; Mikael Johansson; Yonathan Brhane; Ana Fernandez-Somoano; Lambertus A Kiemeney; Michael P A Davies; Shanbeh Zienolddiny; Zhibin Hu; Hongbing Shen Journal: Carcinogenesis Date: 2019-05-14 Impact factor: 4.944
Authors: Christopher M Tracy; Amy J Gray; Jorge Cuéllar; Tanner S Shaw; Alyson C Howlett; Ryan M Taylor; John T Prince; Natalie G Ahn; José M Valpuesta; Barry M Willardson Journal: J Biol Chem Date: 2013-12-27 Impact factor: 5.157