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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?

SUBMITTER: Ziolkowska-Suchanek I

PROVIDER: S-EPMC4550915 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.

Ziółkowska-Suchanek Iwona I Mosor Maria M Gabryel Piotr P Grabicki Marcin M Żurawek Magdalena M Fichna Marta M Strauss Ewa E Batura-Gabryel Halina H Dyszkiewicz Wojciech W Nowak Jerzy J

Scientific reports 20150827

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 ...[more]

PMID: 26310313

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Project description:There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of alpha(1)-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the alpha-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48 x 10(-10), (rs8034191) and 5.74 x 10(-10) (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.

Dataset Information

Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.

Publications

Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.

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