title: Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.
abstract: Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22 (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of our research was to determine the association of IREB2 and FAM13A SNPs with LC and severe/very severe COPD patients. We examined IREB2 variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003, rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking controls). The frequency of the minor IREB2 rs2568494 AA genotype, was higher in LC vs controls (P = 0.0081, OR = 1.682). The FAM13A rs2869967 was associated with COPD (minor CC genotype: P = 0.0007, OR = 2.414). The rs1903003, rs7671167 FAM13A variants confer a protective effect on COPD (both P < 0.002, OR < 0.405). Haplotype-based tests identified an association of the IREB2 AAAT haplotype with LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822). Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles, revealed that the risk for COPD increased with the growing number of the FAM13A risk alleles. OR (95% CI) for carriers of ≥5 risk alleles reached 2.998 (1.8 to 4.97) compared to the controls. This study confirms that the IREB2 variants contribute to an increased risk of LC, whereas FAM13A predisposes to increased susceptibility to COPD.
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.
authors: Iwona
authors: I
authors: Ziółkowska-Suchanek
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.
authors: Maria
authors: M
authors: Mosor
authors: Department of Thoracic Surgery, University of Medical Sciences, 62 Szamarzewskiego Street, 60-569 Poznań, Poland.
authors: Piotr
authors: P
authors: Gabryel
authors: Department of Pulmonology, Allergology and Respiratory Oncology, Poznań University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poland.
authors: Marcin
authors: M
authors: Grabicki
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.
authors: Magdalena
authors: M
authors: Żurawek
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.|Department of Endocrinology, Metabolism and Internal Diseases, Poznań University of Medical Sciences, 49 Przybyszewskiego Street, Poland.
authors: Marta
authors: M
authors: Fichna
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.|Laboratory for Basic Research and Translational Medicine in Vascular Diseases, Clinic of Internal and Vascular Surgery, Poznan University of Medical Sciences, Dluga ½ Street, 61-848 Poland.
authors: Ewa
authors: E
authors: Strauss
authors: Department of Pulmonology, Allergology and Respiratory Oncology, Poznań University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poland.
authors: Halina
authors: H
authors: Batura-Gabryel
authors: Department of Thoracic Surgery, University of Medical Sciences, 62 Szamarzewskiego Street, 60-569 Poznań, Poland.
authors: Wojciech
authors: W
authors: Dyszkiewicz
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.
authors: Jerzy
authors: J
authors: Nowak
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012307:Risk Factors
chemical_list: C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins; D035942:Iron Regulatory Protein 2