Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.
Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.
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DOI：
10.1007/s10552-013-0285-y
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发表时间：
2013-12
期刊：
影响因子：
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通讯作者：
Pankow JS
中科院分区：
文献类型：
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作者：
Prizment AE;Folsom AR;Dreyfus J;Anderson KE;Visvanathan K;Joshu CE;Platz EA;Pankow JS
包括社区动脉粥样硬化风险 (ARIC) 队列在内的许多研究报告称，血浆 C 反应蛋白 (CRP)（一种低度慢性炎症的生物标志物）与结直肠癌风险之间存在正相关，尽管尚不清楚这种关联是否存在因果关系。我们的目的是评估由单核苷酸多态性 (SNP) 创建的 CRP 遗传风险评分 (CRP-GRS) 与结直肠癌风险的关联，并检查血浆 CRP 和 CRP-GRS 与 ARIC 队列中常见癌症的关系。 Cox 比例风险模型用于前瞻性估计总癌、结直肠癌、肺癌、前列腺癌和乳腺癌的风险比 (HR) 和（95% 置信区间，CI），涉及以下方面：1) 1987-2006 年随访的 8,657 名白人中的 CRP-GRS 和 2) 1996-2006 年随访的 7,603 名白人中的对数转换血浆 CRP。加权 CRP-GRS 由位于 CRP、APOC1、HNF1A、LEPR 和全基因组关联研究中鉴定的其他 16 个基因中/附近的 20 个 CRP 相关 SNP 组成。经过多变量调整后，CRP-GRS 的一个标准差增量与结直肠癌风险相关（HR=1.19；95% CI，1.03-1.37），但与任何其他癌症无关。 1 个单位的对数转换血浆 CRP 与总癌、结直肠癌、肺癌和乳腺癌的风险相关：HR (95% CI) 分别为 1.08 (1.01–1.15)、1.24 (1.01–1.51)、1.29 (1.08–1.54) 和 1.27 (1.07–1.51)。在排除随访时间<2 年的受试者后，HR 仍然升高，但除乳腺癌之外的所有癌症均失去了统计学意义。该研究证实了慢性低度炎症在结直肠癌发生中的致病作用。
Many studies, including the Atherosclerosis Risk in Communities (ARIC) cohort, reported a positive association between plasma C-reactive protein (CRP) – a biomarker of low-grade chronic inflammation – and colorectal cancer risk, although it is unclear if the association is causal. Our aims were to assess the associations of a CRP genetic risk score (CRP-GRS) created from single nucleotide polymorphisms (SNPs) with colorectal cancer risk, as well as examine plasma CRP and CRP-GRS in relation to common cancers in the ARIC cohort. Cox proportional hazards models were used to prospectively estimate hazard ratios (HR) and (95% confidence interval, CI) of total, colorectal, lung, prostate, and breast cancers in relation to: 1) CRP-GRS among 8,657 Whites followed in 1987–2006 and 2) log-transformed plasma CRP among 7,603 Whites followed in 1996–2006. A weighted CRP-GRS was comprised of 20 CRP-related SNPs located in/near CRP, APOC1, HNF1A, LEPR and 16 other genes that were identified in genome-wide association studies. After multivariable adjustment, one standard deviation increment of the CRP-GRS was associated with colorectal cancer risk (HR=1.19; 95% CI, 1.03–1.37) but not with any other cancer. One unit of log-transformed plasma CRP was associated with the risk of total, colorectal, lung, and breast cancers: HRs (95% CIs) were 1.08 (1.01–1.15), 1.24 (1.01–1.51), 1.29 (1.08–1.54), and 1.27 (1.07–1.51), respectively. HRs remained elevated, although lost statistical significance for all but breast cancer, after excluding subjects with <2 years of follow-up. The study corroborates a causative role of chronic low-grade inflammation in colorectal carcinogenesis.