Abstract 4201: Associations of pre-diagnostic serum liver enzymes levels with lung cancer risk: results from the Southern Community Cohort Study
Authors: Xu Shuai , Cai Hui , Wu Jie , Yoon Hyung-Suk , Courtney Regina , Shu Xiao-Ou , Blot William J. , Zheng Wei , Cai Qiuyin 
Published: April 2023

Abstract
Introduction: Lung cancer is the leading cause of cancer death in the United States (U.S.). Lung cancer disproportionately affects African Americans (AAs) more than other racial/ethnic groups. Previous studies have linked liver diseases to lung cancer risk; however, few studies have evaluated the associations of circulating liver enzyme levels with lung cancer risk. In this study, we evaluated the associations of the serum alanine transaminase (ALT) and alkaline phosphatase (ALP) levels with the risk of subsequently developing lung cancer.
Methods: We conducted a nested case-control study within the Southern Community Cohort Study, a well-conducted prospective cohort study in the southern U.S. mainly consisting of low-income AAs and European Americans (EAs). We included 552 incident lung cancer cases and 1,039 controls individually matched on age, sex, recruitment sites, and date of blood draw. Baseline serum levels of ALT and ALP were measured using the Beckman Coulter clinical chemistry analyzer. Conditional logistic regression and generalized estimating models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for age, education, household income, body mass index (BMI), smoking status, pack-years, alcohol consumption, physical activity levels, history of chronic obstructive pulmonary disease, hypertension, and diabetes.
Results: Higher serum levels of ALT were associated with a lower overall risk of lung cancer. 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 &lt; 0.01). The inverse association was observed in both AAs and EAs. However, the inverse associations between serum ALT levels and lung cancer risk were more evident among men [ORT3 vs T1 = 0.36 (0.18-0.70)], current smokers [ORT3 vs T1 =0.65 (0.47-0.90)], participants with lower BMI [ORT3 vs T1=0.55 (0.38-0.79)], or lower physical activity [ORT3 vs T1 = 0.55 (0.37-0.83)]. Stratified analyses by time interval between blood collection and lung cancer diagnosis showed that the inverse associations were observed in both those diagnosed within [ORT3 vs T1 =0.48 (0.23-1.00)] and after [ORT3 vs T1 = 0.36 (0.19-0.69)] a median follow up time of 3 years. The serum ALT level was not associated with overall lung cancer; however, higher serum ALP levels were significantly associated with increased lung cancer risk among AA men [ORT3 vs T1 = 1.98 (1.18-3.34)].
Conclusion: Our results indicate that in a predominantly low-income AA and EA population, serum ALT levels may be related to a lower risk of lung cancer. Further studies are warranted to confirm our findings and elucidate the potential underlying mechanisms of the associations.
Citation Format: Shuai Xu, Hui Cai, Jie Wu, Hyung-Suk Yoon, Regina Courtney, Xiao-Ou Shu, William J. Blot, Wei Zheng, Qiuyin Cai. Associations of pre-diagnostic serum liver enzymes levels with lung cancer risk: results from the Southern Community Cohort Study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4201.