Epidemiological studies show COPD, characterized by reduced FEV1, is the most important independent risk factor for susceptibility to lung cancer. When spirometry is routinely measured, co-existing COPD is found in 50-80% of lung cancer cases compared to only 15-20% of randomly selected matched smokers. Recent GWA studies have identified a number of susceptibility loci for COPD, lung function and lung cancer. Several of these loci overlap suggesting that the gene conferring susceptibility to lung cancer might include COPD-related genes.

In this case control study of Caucasian smokers matched for smoking exposure with COPD (n=458), lung cancer (N=454) and healthy smoker status (n=488) we compared the genotype frequencies of 12 loci on chromosomes 1q23, 4q22-24, 4q31, 5p15, 5q33, 6p21, 6q24 and 15q25. All subjects underwent spirometry, completed a modified ATS respiratory questionnaire and gave blood for DNA. Genotyping was done using Taqman real-time PCR (ABI 7900).

We found (1) the AA genotype of CHRNA3/5 (previously associated with lung cancer) conferred susceptibility to lung cancer (OR=1.76, P=0.005) and COPD (OR-1.47, P=0.06), (2) the GG genotype of HHIP (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.59, P=0.006) and lung cancer (OR=0.70, P=0.05) and the CC genotype of FAM13A (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.71, P=0.02) and lung cancer (OR=0.64, P=0.003). These overlapping effects in lung cancer were independent of co-existing COPD.

We conclude the genes conferring susceptibility to lung cancer overlap with those of COPD. Such an observation requires healthy smokers with normal lung function to be used as controls to best identify these COPD-related genes affecting the susceptibility of smokers to lung cancer.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B30.

Copyright © 2010, American Association for Cancer Research
2010