Abstract
Branched-chain amino acids (BCAA) are essential amino acids, and emerging evidence suggests that BCAAs may mediate pathways related to cancer progression, possibly due to their involvement in insulin metabolism. We investigated the association between dietary intake of BCAAs with colorectal cancer risk in three prospective cohorts: the Nurses' Health Study I [(NHS), number of participants (n) at baseline = 77,017], NHS II (n = 92,984), and the Health Professionals Follow-up Study [(HPFS) n = 47,255]. Validated food frequency questionnaires were administered every 4 years and follow-up questionnaires on lifestyle biennially. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models. Pooled HRs were obtained using random effect models. After up to 28 years of follow-up, 1,660 cases were observed in NHS, 306 in NHS II, and 1,343 in HPFS. In multivariable adjusted models, we observed a weak inverse association between BCAA intake and colorectal cancer [highest vs. lowest quintile, pooled HR including all three cohorts (95% CI): 0.89 (0.80-1.00), P (trend) = 0.06, HR per standard deviation (SD) increment 0.95 (0.92-0.99)]. However, after including dairy calcium to the models, BCAA intake was no longer associated with risk of colorectal cancer [HR 0.96 (0.85-1.08), P (trend) = 0.50, HR per SD increment 0.97 (0.93-1.01)]. We did not find evidence that higher dietary BCAA intake is associated with higher risk of colorectal cancer. As this is the first prospective study to examine the association between BCAA intake and colorectal cancer, our findings warrant investigation in other cohorts.