Early adulthood body mass index, cumulative smoking, and esophageal adenocarcinoma survival.

Background: Smoking and obesity are esophageal adenocarcinoma (EAC) risk factors. However, the same risk factors may also affect biological aggressiveness and cancer outcomes. Our study evaluated the combined effects of early-adulthood obesity and cumulative smoking on the EAC survival. Patients and

Methods: In two EAC cohorts, Toronto (TO; N=235) and Boston (BO; N=329), associations between early adulthood body mass index (EA-BMI), BMI at 1year prior to diagnosis (BMI-1), and smoking with overall survival (OS) were assessed using Cox proportional hazard models, adjusted for relevant covariates.

Results: Both cohorts were predominantly Caucasian (89%), male (88%), ever-smokers (73%) with locally advanced/metastatic EAC (78%), and good ECOG performance status (90%); median packyears was 34; median EA-BMI, 24; median BMI-1, 25. No relationships with survival were found with BMI-1. For smoking and EA-BMI, TO, BO, and combined TO-BO analyses showed similar associations: smoking conferred worse OS in the combined TO-BO cohort, with adjusted hazard ratios (aHR) of 1.22 (95%CI: 1.15-1.43;p<0.0001) for each 20 pack-year increase. Likewise, EA-BMI ≥25 was associated with worse OS (EA-BMI of 25-<30, aHR=1.84,95%CI: 1.37-2.48; and EA-BMI>30, aHR=2.78, 95%CI: 1.94-3.99). Risk of death was also increased in remotely underweight patients with EA-BMI<18.5 (aHR=2.03,95%CI: 1.27-3.24), when compared to normal-EA-BMI (18≤EA-BMI<25).

Conclusions: Two key modifiable behaviors, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk in two North American cohorts of EAC patients.