William J. Blot

Previous studies have linked liver diseases to lung cancer (LC) risk; however, few studies evaluated the associations of circulating liver enzyme levels with LC risk. We conducted a study of 353 incident LC cases and 646 matched controls with baseline serum alanine aminotransferase (ALT) and of 548 cases and 1032 matched controls with baseline serum alkaline phosphatase (ALP) nested within the Southern Community Cohort Study. Conditional logistic regression and generalized linear models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among all study participants and by stratification of potential effect modifiers. Most participants had clinically normal liver enzyme levels. Higher serum ALT levels were associated with reduced LC risk. Compared with the lowest tertile, participants in the second and third tertiles had OR (95% CI) of 0.74 (0.48–1.14) and 0.47 (0.28–0.78) (Ptrend < .01), respectively. The inverse association was observed in African Americans (AAs) and European Americans, which was especially prominent among men, and was seen in both those diagnosed within [ORT3 versus T1 = 0.41 (0.19–0.88)] and beyond [ORT3 versus T1 = 0.35 (0.17–0.73)] a median follow-up time of 39 months. Higher serum ALP levels were associated with increased LC risk among AA men only [ORT3 versus T1 = 2.01 (1.19–3.39)] (Ptrend < .01). Our results indicate that in a predominantly low-income American population, higher serum ALT levels may be related to lower LC risk. Further studies are warranted to confirm our findings and elucidate the potential underlying biological mechanisms of the associations.

Supplemental Table 2. Median and SD of the log distribution for smoking-related urinary biomarkers overall

Supplemental Table 4. Characteristics for study participants in Southern Community Cohort, by race

Supplemental Table 5. Geometric mean of Biomarkers by Race/Ethnicity Controls and in the overall study

Background:After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans.Methods:In a nested case–control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1–3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk.Results:TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10–1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03–1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL.Conclusions:Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years.Impact:Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

Supplemental Table 4. Characteristics for study participants in Southern Community Cohort, by race

Supplemental Table 7. Association of urinary biomarkers and lung cancer risk in Southern Community Cohort participants stratified by histologic cell-type

Supplemental Table 6. Geometric mean of Biomarkers in cases and controls stratified by Race/Ethnicity, adjusted for creatinine

Supplemental Table 1. Coefficients of Variation for Biomarker analysis

Supplemental Table 7. Association of urinary biomarkers and lung cancer risk in Southern Community Cohort participants stratified by histologic cell-type