炎性标志物与炎症性肠病患者结肠癌风险相关

《临床胃肠病和肝病学》1月6日在线发表的一项前瞻性研究显示，C反应蛋白(CRP)水平和红细胞沉降率(ESR)升高的炎症性肠病(IBD)患者，其结直肠癌(CRC)风险显著增加，因此，这两个指标可作为结肠癌风险的标志物(Clin. Gastroenterol.Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030])。

波士顿麻省总医院胃肠病专家Ashwin Ananthakrishnan医生及其同事依据中位CRP水平和中位ESR的不同，分别将3,145 例和4,008例IBD患者分为四分位数，然后进行随访，中位随访时间6年。多变量分析显示，高CRP分位数患者的CRC风险显著增加(趋势检验P=0.017)，高ESR也与CRC高风险呈独立相关 (趋势检验P=0.007) 。

研究者称，上述相关性以及其他临床变量有助于患者风险分层。确认患者风险程度非常重要，持续强化监测策略可使CRC高风险患者受益，而对于低风险患者，可考虑减少结肠镜检查频次。每位患者的炎症严重程度或有助于制定个体化监测方案，甚至还有益于治疗应答等其他结局的监测。

校正年龄、性别、种族、IBD类型及其他因素后，最高CRP四分位数患者CRC风险是最低四分位数患者的2倍(OR，2.72；95% CI，0.95~7.76)。无论男性还是女性、克罗恩病还是溃疡性结肠炎患者，这一关联强度均相似。

同样，最高ESR四分位数患者CRC风险也是最低四分位数患者的2倍(OR，2.06；95% CI，1.14~3.74)，溃疡性结肠炎及男性患者关联性最强。

每个分位数患者中位CRP值分别为0.8、2.7、7.5和32.8 mg/L，中位ESR值分别为7、14、25和50 mm/h。

总体上，CRP队列和ESR队列中分别有33例和102例患者发展为结直肠癌，确诊时中位年龄为55岁。中位CRP检测次数为3次，中位ESR检测次数为6次。半数以上患者为女性，大多数为白人，溃疡性结肠炎患者略多于克罗恩病患者。

校正结肠镜检查次数、医疗服务利用强度、类固醇使用情况以及其他因素后，无论CRP队列还是ESR队列，上述结果任然如此。

该研究由美国国立卫生研究院(NIH)资助。研究者无利益冲突披露。

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By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol.Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. AshwinAnanthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.