This study developed and validated a specific risk prediction model of lung cancer for African-Americans. Smoking cessation (former smokers), pack-years smoked, prior COPD, no history of hay fever, and exposure to asbestos and wood dust were significant risk factors in this minority population. Internal and external validation results showed that our model discriminates well between cases and controls, except for a subgroup of early-onset lung cancer cases. The model that we propose for African-Americans outperformed a similar lung cancer risk model developed primarily for white populations.
In our comparison of risk factors in the African-American model and those developed using white-only data, we observed similarities and differences in distribution of risk factors among the two racial groups. In our study, 41% of study cases presented with advanced (stage IV) lung cancer. In contrast, 24.3% of the white cases in the entire parent study population had stage IV lung cancer at their initial examination. These differences in stage at time of presentation may be influenced not only by disparities in socio-economic factors, health insurance or access to health care in African-American populations (16
), but by biologic factors as well. Difference exist in pulmonary function among different racial groups (17
): African-Americans have lower forced vital capacity, lower forced expiratory volume, and higher percentage of forced expiratory capacity expired in 1 second compared to whites. Adenocarcinoma was the most common histology diagnosed in African-American women, whereas African-American men presented with squamous cell carcinoma as frequently as adenocarcinoma. Previously (3
), we showed that 51% of white cases presented with adenocarcinoma followed by squamous cell carcinoma (22%).
Most of our African-American current smokers smoked between a half pack and a full pack (10−27 cigarettes) per day, similar to levels reported by Haiman et al. (18
) and less than levels reported for whites. In our parallel case-control study in whites, the average number of cigarettes per day was 28.1 in cases compared with 26.4 in controls (P
≤ 0.001; ref. 3
). In this study, cases who smoked ≥20 cigarettes per day exhibited about a 4-fold increase in risk (OR, 3.94; 95% CI, 2.26−6.87). Stellman et al. (19
) reported that the risk of lung cancer for African-Americans who smoked >20 cigarettes per day was five times higher than that for African-American women and six times higher than men who smoked ≤20 cigarettes per day.
The use of mentholated cigarettes is believed to increase the risk of lung cancer because these cigarettes have higher tar content, generate higher levels of carcinogens, and facilitate the absorption of carbon monoxide (20
). It has also been suggested that the anesthetic properties and cooling effects of menthol may lead to deeper inhalation and longer retention, which may result in increased exposure to carcinogenic substances present in tobacco smoke (21
). But the association between mentholated cigarette consumption and lung cancer is controversial (19
). In a recent review, Werley et al. (21
) reported that 70% to 80% of African-American men and women chose mentholated cigarettes. We observed lower percentages of menthol use (41−60%) in our study among African-American men and women smokers. In our analysis, we observed no significant risks of lung cancer among former or current smokers who reported smoking mentholated cigarettes (OR range, 0.69−0.99) and our data suggested a possible protective effect of mentholated cigarettes for current smokers. Sidney et al. (26
) reported an increased risk in men who smoke mentholated cigarettes, whereas others (19
) reported a nonsignificant protective effect in both whites and African-Americans. A recent study by Murray et al. (27
) also found no evidence of a higher risk of death from lung cancer in smokers who smoked mentholated cigarettes.
African-American men and women who reported longer durations of smoking cessation had lower risks of lung cancer. Others have reported similar declines in risk in African-American populations (19
). We further observed that men who quit smoking after age 30 remained at substantially higher risks of lung cancer. A cohort study of 34,439 male British physicians reported that the maximum years of life expectancy gained were when cases stopped smoking before the age of 30 (29
). Between 10% and 15% of all cases with lung cancer are never smokers (30
); however, we observed a much lower proportion (2.4%) in our male cases.
We identified exposures to asbestos and wood dusts as significant risk factors for lung cancer in African-Americans. Such an association in African-Americans has been well documented previously (31
). Our observations were similar to those in previous reports of asbestos exposure in whites (33
) and of exposure to wood dusts in a subset of this population previously studied (34
We also noted that some specific occupational exposures (SVFs and toluene and/or xylene) were associated with lung cancer among African-Americans, although these risks were not significant in our final multivariable model. Pohlabeln et al. (36
) reported an association between exposure to man-made vitreous fibers (i.e., SVFs) and lung cancer after adjusting for smoking and asbestos exposure. All SVFs have essentially the same oncogenic potential. Some studies, however, may not show a statistically significant association because they lack sufficient statistical power to detect the small level of incremental risk associated with a fiber that clears rapidly from the lungs (37
). Cohort studies have shown an increase in mortality due to lung cancer in whites after exposure to toluene (40
). However, in our parallel study in whites (3
), we identified a nonsignificant association between exposure to toluene and/or xylene and risk of lung cancer, although the prevalence of such exposure in cases with lung cancer (30.1%) was similar to that in African-American (34.4%) cases.
The risks associated with COPD that we report for African-Americans in our current study are substantially higher than those we reported previously for whites (OR, 1.7−2.65; refs. 3
). For white cases, the prevalence of COPD was 22.4% and 9.4% in controls (3
). However, in this analysis, the prevalence of COPD was 16.5% among the African-American cases and only 2% among controls. These differences reflect national rates. The 2002 COPD data from the American Lung Association report that the prevalence rates for chronic bronchitis in the U.S. population are 45.7/1,000 for whites and 46.1/1,000 for blacks (42
). National incidence rates for emphysema are 17.1/1,000 for whites and 8.3/1,000 for blacks (42
). Hnizdo et al. (43
) reported that the percent prevalence of airflow obstruction for the total working population was 10.7% for Caucasians and 7.5% for African-Americans. Littman et al. (44
) reported that independent of smoking history, smokers (mostly white) with a history of chronic bronchitis and/or COPD have a higher risk of lung cancer, a finding confirmed in other studies (45
The protective effect of hay fever that we observed in the minority group is similar to our previous findings for whites (33
) and also previously reported in a mixed ethnic population of never smokers (47
). Borderline significant protective effects of hay fever were also noted by Osann (48
) in women with lung cancer. However, a later study by Osann et al. (49
) found no significant association between hay fever and the risk of small cell lung cancer among women, although the Osann et al. study focused only on women with small cell lung cancer (49
In this analysis, we did observe an elevated but not statistically significant association between family history and lung cancer. In our previous analyses of white cases and controls, we observed increased risks of lung cancer for never smokers (OR, 2.00) and former smokers (OR, 1.59) with a family history of any cancer and among current smokers (OR, 1.51) with a family history of smoking-related cancers (3
). Cote et al. (13
) reported that first-degree relatives of African-American individuals with early-onset lung cancer have a greater risk of lung cancer than whites, and cigarette smoking further increased these risks. We similarly stratified African-American cases by age at onset of disease (data not shown) but observed no increased risk among cases with early-onset (age ≤50 years) disease.
Cassidy et al. (50
) reviewed the history of risk prediction models and particularly emphasize lung cancer risk prediction models and their importance to lung cancer research. In our lung cancer risk model for white lung cancer patients and controls (3
), the controls, unlike our minority controls, were matched to their respective patients on smoking status. Because of the large number of white participants, we were able to construct and internally validate separate models for never, former, and current smokers. Some of the risk factors included in the three models previously published (1
) overlapped with those found to be statistically significant in our minority risk models (i.e., smoking-related measures, exposures to asbestos or wood dusts, emphysema, and no previous hay fever). However, the level of risk may differ depending on the type and level of exposure. Therefore, these three risk models may not be applicable to minority populations.
Indeed, our model validation results showed that the ability of the Spitz model to discriminate between minority patients and controls was moderate (67% for African-Americans smokers), whereas the group-specific models showed better discriminatory power (79%). The Spitz model included smoking-related variables (age at smoking cessation for former smokers and pack-years smoked for current smokers) but could not include a risk estimate for smoking status because it was a matching variable. The inclusion of smoking status in the minority risk models could have further increased the discriminatory power that we observed. In the model based on white patients, asbestos and wood dust occupational exposures were significant. In the African-American model, asbestos and wood dusts were also included. Moreover, family histories of any cancer and of smoking-related cancers were included in the Spitz model for whites (3
), but family history of cancer was not a statistically significant factor in our minority models.
The results from the validation analyses indicate that our lung cancer prediction model for African-Americans can prove helpful by providing more precise estimates compared with the existing risk prediction models and further highlight the need for ethnic-specific lung cancer risk prediction models. However, the sample size for validation was small.
The other limitations of our study include the fact that our study was hospital based and the controls were drawn only from the metropolitan area of Houston, Texas; therefore, the results may vary in other geographic locations. Because the sample size of the study was small, the precision of our OR estimates is not as small compared with those in our white cases of lung cancer. We may be able to see better results with larger data sets or data sets where participants are not selectively enrolled based on particular criteria (such as gender or early age at diagnosis). Further, we were unable to confirm self-reported comorbidities or exposures. However, as noted by Cassidy et al. (50
), a good risk prediction tool for lung cancer should include other factors in addition to smoking and age and our minority risk models included occupational exposures, comorbidities, and smoking phenotypes. Therefore, our results provide a foundation for lung cancer risk models for minority populations.
This study shows that African-Americans have risk factors for lung cancer that also occur in whites. However, the level of risk may differ depending on the type and level of exposure. African-Americans have a higher mortality due to lung cancer compared with whites and will benefit from early detection programs, including those using risk prediction tools. These findings highlight the importance of conducting further ethnic-specific analyses of disease risk.