Long Lu, Yang Wanshui, Liu Li, Tobias Deirdre K, Katagiri Ryoko, Wu Kana, Jin Lina, Zhang Fang-Fang, Luo Xiao, Liu Xing, Ogino Shuji, Chan Andrew T, Meyerhardt Jeffrey A, Giovannucci Edward, Zhang Xuehong
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Int J Cancer. 2021 May 15;148(10):2471-2480. doi: 10.1002/ijc.33449. Epub 2020 Dec 29.
Branched-chain amino acids (BCAAs), including leucine, isoleucine and valine, may potentially influence cancer progression by various mechanisms including its role in insulin resistance. However, the association of BCAAs with survival among patients with established colorectal cancer (CRC) remains unclear. We evaluated the associations between postdiagnostic BCAA intake with CRC-specific mortality and overall mortality among 1674 patients with nonmetastatic CRC in the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire. Multivariable hazard ratios (HRs) were calculated using Cox proportional-hazards regression model after adjustment for tumor characteristics and potential confounding factors. Comparing the highest with the lowest quartile intake of postdiagnostic total BCAA, the multivariable HRs were 1.18 (95% confidence interval [CI], 0.75-1.85, P for trend = .46 across quartiles) for CRC-specific mortality and 1.30 (95% CI, 1.01-1.69, P for trend = .04) for all-cause mortality. The multivariable HRs (the highest vs the lowest quartile) for all-cause mortality were 1.33 (95% CI, 1.03-1.73, P = .02) for valine, 1.28 (95% CI, 0.99-1.66, P for trend = .05) for leucine and 1.25 (95% CI, 0.96-1.61, P for trend = .06) for isoleucine. No statistically significant associations with each of the BCAA intake were observed for CRC-specific mortality (all P for trend > .30). Our findings suggest positive associations between higher intake of dietary BCAAs and risk of all-cause mortality in CRC patients. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated.
支链氨基酸(BCAAs),包括亮氨酸、异亮氨酸和缬氨酸,可能通过多种机制影响癌症进展,包括其在胰岛素抵抗中的作用。然而,BCAAs与已确诊的结直肠癌(CRC)患者生存率之间的关联仍不明确。我们在护士健康研究和卫生专业人员随访研究中,评估了1674例非转移性CRC患者诊断后BCAA摄入量与CRC特异性死亡率和总死亡率之间的关联。患者完成了一份经过验证的食物频率问卷。在调整肿瘤特征和潜在混杂因素后,使用Cox比例风险回归模型计算多变量风险比(HRs)。将诊断后总BCAA摄入量的最高四分位数与最低四分位数进行比较,CRC特异性死亡率的多变量HR为1.18(95%置信区间[CI],0.75 - 1.85,四分位数间趋势P = 0.46),全因死亡率的多变量HR为1.30(95% CI,1.01 - 1.69,趋势P = 0.04)。缬氨酸全因死亡率的多变量HR(最高四分位数与最低四分位数相比)为1.33(95% CI,1.03 - 1.73,P = 0.02),亮氨酸为1.28(95% CI,0.99 - 1.66,趋势P = 0.05),异亮氨酸为1.25(95% CI,0.96 - 1.61,趋势P = 0.06)。未观察到CRC特异性死亡率与每种BCAA摄入量之间存在统计学显著关联(所有趋势P > 0.30)。我们的研究结果表明,CRC患者饮食中BCAAs摄入量较高与全因死亡风险呈正相关。这些发现需要得到证实,并且需要阐明这种关联背后的潜在机制。