SAT-134 Association between Serum Branched-Chain Amino Acids and Cancer Risk: The Hong Kong Diabetes Register (HKDR)

Background: Hyperglycemia and obesity are major risk factors of many types of cancer. Branched-chain amino acids (BCAA including leucine, isoleucine and valine) are essential amino acids that regulate energy homeostasis. Serum BCAA levels are determined by dietary intake and tissue metabolism. Contrary to claims that BCAA-rich diet/supplements may improve weight and insulin resistance, recent data suggest that BCAA may contribute to tumorigenesis. We examined the association of serum BCAA with cancer risk in a prospective Chinese cohort with type 2 diabetes (T2D). Methods: Between 1995 and 2007, after written consents, all patients had structured assessment including eye/feet examination and blood/urine tests. We measured serum total BCAA in 2607 patients who were cancer-free at baseline and with available stored serum samples, who subsequently developed cancer after one year of enrolment into the HKDR. We performed Cox proportional hazards models with serum BCAA as the predictor variable, adjusting for age, sex, duration of T2D, cardiovascular risk factors (HbA(1c), systolic blood pressure, LDL-cholesterol, triglyceride and body mass index) and drug usage. The primary outcome was the first occurrence of any cancer with data censored on 30 June 2017. Results: After a mean±SD follow-up of 13.4±4.2 years, 289 (11.1%) patients developed cancer, mainly from the digestive tract (n=138 including 54 colorectal, 35 liver and 14 pancreatic), genitourinary tract (n=47), lung (n=45) and breast (n=21). The median (interquartile range) serum BCAA at baseline was not statistically different between patients with incident cancer and those without (612.3 [528.5-716.3] vs. 603.7 [522.7-706.3] µmol/L; P=0.48). In the unadjusted model of the total cohort, every doubling of serum BCAA was not associated with any increased risk of primary outcome (hazard ratio [HR] 0.86, 95% confidence interval 0.68-1.07). In subgroup analysis, the corresponding HR for genitourinary cancer was 1.38 (0.92-2.06), which was accentuated to 1.65 (1.08-2.54; P=0.022) after adjustment for aforementioned covariates. By contrast, the associations were not significant for digestive tract (0.9, 0.65-1.24), colorectal (0.92, 0.57-1.48), liver (1.14, 0.62-2.09), pancreatic (0.67, 0.21-2.15), lung (0.69, 0.37-1.31) and breast (0.62, 0.25-1.53) cancer, adjusting for age, sex and duration of T2D. There were no significant BCAA-sex interactions in all analyses. Conclusions: In Chinese T2D patients, high serum BCAA level was independently associated with an excess risk of incident genitourinary cancer, whereby validation in a larger cohort is needed. Although the directions of the associations with different cancer types were mixed, these were consistent with current evidence which shows that the BCAA metabolism reprogramming in cancer is complex and likely dependent on the tissue of origin. Funding: HKASO, HKSEMR