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Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.

Airflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American populationTo describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and to evaluate their impact on the management and outcome of lung cancer.Medical records of 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan, were reviewed. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment, and outcome. Computed tomographies (CT) of the chest about the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CTs and/or airflow obstruction by spirometry.There were no differences by sex for age at lung cancer diagnosis (P = .78) and tumor histology (P = .43). The men were more likely to present at a later stage of lung cancer diagnosis compared with the women (P = .04), and the women were more likely to have surgery than the men (P = .03). Overall, 94% of the men and 78% of the women in this population had spirometry and/or CT evidence of COPD. The men were somewhat more likely to have COPD diagnosed by either CT or spirometry than were the women (P = .06), but the Global Obstructive Lung Disease Classification scores did not differ by sex among those with spirometry-diagnosed COPD (P = .34). Seventy-eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (P = .03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (P = .82) or emphysema diagnosis (P = .51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (P = .30 and P = .06, respectively), nor did treatment modality (P = .54 and P = .10, respectively). Patients with lung cancer and with COPD, diagnosed either via spirometry or CT, did not show an increased risk of death compared with patients with lung cancer and without COPD after adjusting for age at diagnosis, sex, and stage (hazard ratio, 1.31 [95% CI, 0.68-2.53]).There is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.