Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort

Background: Bariatric surgery reduces cancer risk in populations with obesity. It is unclear if weight loss alone or metabolic changes related to bariatric surgery cause this effect. Objective: We evaluated the relationship between surgical weight loss and serum biomarker changes with incident cancer in a bariatric surgery cohort. Setting: Ten U.S. clinical facilities. Methods: The Longitudinal Assessment of Bariatric Surgery 2 (LABS-2) is a prospective multicenter cohort (n = 2458, 79% female, mean age = 46). We evaluated weight and serum biomarkers, measured preoperatively and 1 year postoperatively, as predictors for incident cancer. Associations were determined using Cox proportional hazards models adjusting for weight loss, age, sex, education, and smoking history. Results: Over 8759 person-years of follow-up, 82 patients reported new cancer diagnosis (936 per 100,000 person-years, 95% confidence interval [CI]: 749–1156). Cancer risk was decreased by approximately 50% in participants with 20% to 34.9% total weight loss (TWL) compared with <20% TWL (hazard ratio [HR] =. 49, 95%CI:. 29–.83). Reduced cancer risk was observed with percent decrease from baseline for glucose (per 10%, HR =. 94, 95%CI:. 90–.99), proinsulin (per 20%, HR =. 95, 95%CI:. 93–.98), insulin (per 30%, HR =. 97, 95%CI:. 96–.99), and leptin (per 20%, HR =. 81, 95%CI:. 68–.97), and per 15% percent increase in ghrelin (HR =. 94, 95%CI:. 29–.83). Conclusions: After bariatric surgery, cancer risk is reduced >50% when weight loss exceeds 20% TWL compared with patients with <20% TWL. Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk.