Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Int J Cancer. 2020 Aug 15;147(4):920-930. doi: 10.1002/ijc.32844. Epub 2020 Jan 11.
Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45-0.99, p = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41-1.29, p = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92-2.60, p = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01-3.84, p = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.
虽然先前的研究表明性激素在结直肠癌(CRC)的发病机制中可能起作用,但尚无研究检查循环性激素与 CRC 患者生存之间的关系。我们前瞻性地评估了 609 例 CRC 患者(370 名男性和 239 名绝经后未接受激素治疗的女性)在采集血液时的雌酮、雌二醇、游离雌二醇、睾丸激素、游离睾丸激素和性激素结合球蛋白(SHBG)的预测血浆浓度与 CRC 特异性和总死亡率之间的关系。使用 Cox 比例风险回归估计多变量风险比(HR)和 95%置信区间(CI)。我们在男性中发现了 174 例死亡(83 例 CRC 特异性死亡),在女性中发现了 106 例死亡(70 例 CRC 特异性死亡)。在男性中,循环游离睾丸激素水平较高与总死亡率(最高与最低三分位数,HR=0.66,95%CI,0.45-0.99,p=0.04)和可能的 CRC 特异性死亡率(HR=0.73,95%CI,0.41-1.29,p=0.27)呈负相关。我们通常观察到其他性激素呈非显著负相关,并且 SHBG 与男性患者的 CRC 特异性死亡率呈正相关。然而,在女性中,我们发现雌酮与总死亡率(HR=1.54,95%CI,0.92-2.60,p=0.11)和 CRC 特异性死亡率(HR=1.96,95%CI,1.01-3.84,p=0.06)呈阳性关联,具有提示意义。总雌二醇、游离雌二醇和游离睾丸激素通常与女性患者的死亡率升高呈阳性关联,但无统计学意义。这些发现表明内源性性激素在 CRC 预后中可能起作用,值得进一步研究。