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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.

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