Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals.

Although aspirin has been considered a promising agent for prevention of colorectal cancer (CRC), recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of CRC may benefit from aspirin remains unknown. We used a 95-variant CRC polygenic risk score (PRS) to explore the association between genetic susceptibility to CRC and aspirin use in a prospective study of 12,609 individuals of European descent aged ≥70 years, enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) double-blinded, placebo-controlled randomized trial (RCT). Cox proportional hazards models were used to assess the association of aspirin use on CRC, as well as the interaction between the PRS and aspirin treatment on CRC. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident CRC. Aspirin assignment was not associated with incidence of CRC overall (hazard ratio [HR]=0.94, 95% confidence interval (CI) 0.68–1.30) or within strata of PRS (p for interaction=0.97). However, the PRS was associated with an increased risk of CRC (HR=1.28 per standard deviation [SD], 95% CI 1.09–1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR=1.85, 95% CI 1.08–3.15). In a prospective RCT of older individuals, a PRS is associated with incident CRC risk, but aspirin use was not associated with a reduction of incident CRC, regardless of baseline genetic risk.

尽管阿司匹林一直被认为是预防结直肠癌（CRC）的一种有前景的药物，但近期数据表明，在老年人中其并无益处。一些CRC风险较高的个体是否可能从阿司匹林中获益仍不清楚。我们在一项针对12609名年龄≥70岁的欧洲血统个体的前瞻性研究中，使用了一个包含95个变异的CRC多基因风险评分（PRS）来探究CRC的遗传易感性与阿司匹林使用之间的关联，这些个体参与了ASPREE（阿司匹林减少老年人事件）双盲、安慰剂对照随机试验（RCT）。考克斯比例风险模型被用于评估阿司匹林使用与CRC之间的关联，以及PRS和阿司匹林治疗对CRC的相互作用。在中位随访4.7年期间，143名参与者被诊断为新发CRC。阿司匹林用药与总体CRC发病率无关（风险比[HR]=0.94，95%置信区间[CI]为0.68 - 1.30），在PRS各分层内也无关（相互作用的P值=0.97）。然而，PRS与CRC风险增加相关（每标准差[SD]的HR = 1.28，95% CI为1.09 - 1.51）。PRS分布处于最高五分位数的个体与处于最低五分位数的个体相比，风险高85%（HR = 1.85，95% CI为1.08 - 3.15）。在一项针对老年人的前瞻性RCT中，PRS与新发CRC风险相关，但无论基线遗传风险如何，阿司匹林的使用与新发CRC的减少无关。