Spanish Centre for Pharmacoepidemiologic Research, c/ Almirante 28, 2°, 28004, Madrid, Spain.
Epidemiology, Bayer AG, Müllerstr. 178, 13353, Berlin, Germany.
BMC Cancer. 2017 Sep 7;17(1):637. doi: 10.1186/s12885-017-3594-9.
Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease.
We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up.
Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19).
Patients starting low-dose aspirin therapy have a reduced risk of Stages B-D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years' therapy.
临床试验人群的证据表明，低剂量阿司匹林可降低结直肠癌（CRC）的风险。这种风险的部分降低可能是由于对转移性疾病的保护。
我们研究了新使用低剂量阿司匹林（75-300mg）的人群中 CRC 的风险，包括诊断时的风险分期。我们利用健康改进网络（The Health Improvement Network），开展了一项队列研究，并进行了嵌套病例对照分析。2000 年至 2009 年，我们从年龄在 40-89 岁之间、无癌症的人群中确定了两个队列（每组 170336 人）：i）新使用低剂量阿司匹林的人群；ii）在随访开始时未使用低剂量阿司匹林的人群，通过年龄、性别和既往初级保健医生就诊次数进行匹配。患者随访时间最长达 12 年，以确定 CRC 的发病情况。通过发病率密度抽样选择了 10000 名频率匹配的对照，其中比值比是发病率比（RR）的无偏估计值。计算了 95%置信区间内的 RR。为了说明在随访期间暴露情况的变化，低剂量阿司匹林的使用被分类为“治疗中”，独立于基线暴露状态。
当前使用低剂量阿司匹林（在索引日期或之前的 90 天内使用）的患者 CRC 风险显著降低，RR 为 0.66（95%CI 0.60-0.74）。在所有年龄组中，这种风险降低都很明显，与剂量、适应证、性别、CRC 位置或病死率无关。治疗过程中持续存在降低风险的情况，且所有低剂量阿司匹林剂量均存在这种情况。阿司匹林适应证的 RR 分别为 0.71（0.63-0.79）和 0.60（0.53-0.68），用于原发性和继发性心血管保护。在有分期信息的病例中（n=1421），当前使用低剂量阿司匹林的 RR 为 Dukes A 期 CRC 0.94（0.66-1.33），Dukes B 期 0.54（0.42-0.68），Dukes C 期 0.71（0.56-0.91），Dukes D 期 0.60（0.48-0.74）。治疗 5 年后，Dukes A 期 CRC 的 RR 为 0.53（0.24-1.19）。
开始低剂量阿司匹林治疗的患者 CRC 的 Dukes B-D 期风险降低，表明低剂量阿司匹林在已建立的 CRC 进展中发挥作用；5 年后 Dukes A 期 CRC 的风险可能显著降低。
