Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies.
Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies.
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DOI：
10.1158/1940-6207.capr-11-0113
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Chan AT
中科院分区：
文献类型：
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作者：
Lee JE;Baba Y;Ng K;Giovannucci E;Fuchs CS;Ogino S;Chan AT
他汀类药物的使用被认为可以降低结直肠癌的风险，但证据仍然不一致。这可能部分是由于不同肿瘤位置或结直肠癌分子亚型的不同关联。在两项大型前瞻性队列研究中，我们根据肿瘤位置、KRAS突变状态、微卫星不稳定性(MSI)状态、Ptgs2(环氧合酶-2，COX-2)表达或CpG岛甲基化表型(CIMP)状态来检验他汀类药物的使用与结直肠癌风险之间的关系。我们将考克斯回归应用于竞争风险分析。我们在1990-2006年间发现了1818例结直肠癌。与不使用他汀类药物的患者相比，目前使用他汀类药物与结肠癌(RR=1.1 0，95%CI=0.94~1.2 9)和结肠癌(RR=0.99，95%CI=0.86~1.14)无关，但与直肠癌呈负相关(RR=0.5 9，95%CI=0.41~0.84，P均<0.0.001)。当我们检查KRAS突变状态的分层关联时，我们发现与KRAS突变的癌症没有关联(RR=1.20，95%CI=0.87至1.67)，但观察到KRAS野生型癌症之间可能存在负关联(RR=0.80，95%CI=0.60至1.06，P为异质性=0.06)。这种关联在Ptgs2表达、微卫星不稳定(MSI)状态或CIMP状态方面没有显著差异。目前他汀类药物的使用与整体结直肠癌的风险无关。他汀类药物的使用可能与直肠癌或KRAS野生型结直肠癌的风险降低有关，这一可能性需要进一步证实。
Use of statins is hypothesized to reduce colorectal cancer risk, but the evidence remains inconsistent. This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer. We examined the association between statin use and colorectal cancer risk according to tumor location, KRAS mutation status, microsatellite instability (MSI) status, PTGS2 (cyclooxygenase-2, COX-2) expression, or CpG island methylator phenotype (CIMP) status in two large prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. We applied Cox regression to a competing-risks analysis. We identified 1818 colorectal cancers during 1990-2006. Compared to non-users, current statin use was not associated with colorectal cancer (Relative Risk [RR] = 0.99, 95% CI = 0.86 to 1.14) or colon cancer (RR = 1.10, 95% CI = 0.94 to 1.29), but was inversely associated with rectal cancer (RR = 0.59, 95% CI = 0.41 to 0.84, P for heterogeneity <0.001). When we examined the association within strata of KRAS mutation status, we found no association with KRAS-mutated cancers (RR = 1.20, 95% CI = 0.87 to 1.67), but did observe a possible inverse association among KRAS-wildtype cancers (RR = 0.80, 95% CI = 0.60 to 1.06, P for heterogeneity=0.06). The association did not substantially differ by PTGS2 expression, microsatellite instability (MSI) status or CIMP status. Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS-wild type colorectal cancer requires further confirmation.