A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis
A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis
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DOI：
10.1177/2050640615581577
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发表时间：
2016-02
影响因子：
6
通讯作者：
A. Wannhoff;T. Folseraas;M. Brune;C. Rupp;Kilian Friedrich;J. Knierim;K. Weiss;P. Sauer;C. Flechtenmacher;P. Schirmacher;W. Stremmel;J. Hov;D. Gotthardt
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作者：
A. Wannhoff;T. Folseraas;M. Brune;C. Rupp;Kilian Friedrich;J. Knierim;K. Weiss;P. Sauer;C. Flechtenmacher;P. Schirmacher;W. Stremmel;J. Hov;D. Gotthardt
原发性硬化性胆管炎（PSC）患者发生胆道癌的风险增加，血清癌胚抗原（CEA）水平可用于筛查。目的探讨癌胚抗原（CEA）在原发性胆管癌（PSC）筛查中的应用，并分析岩藻糖基转移酶（FUT）2和3基因变异对血清CEA水平的影响。方法在一项回顾性队列分析中，我们评估了226例PSC患者（包括19例胆道恶性肿瘤）的CEA水平，并研究了FUT 2和FUT 3 SNP如何影响CEA水平。进行受试者工作特征（ROC）分析，并根据Youden指数确定临界值。对照组包括240例患者，其中28例为胆道恶性肿瘤。结果无癌组CEA浓度中位数（1.4ng/mL）低于有癌组（2.0ng/mL）（P = 0.014）; ROC分析显示曲线下面积（AUC）为0.671，最佳截止值为3.2 ng/mL。FUT 2变体rs601338（G428 A）与CEA水平相关，并且在遗传上不能表达CA 19 -9的患者亚组中效果最显著。如果分别对野生型（AUC：0.731）和纯合突变型（AUC：0.816）G428 A进行ROC分析，则AUC改善。在对照组中证实了FUT 2对CEA的影响。结论CEA对PSC患者的胆道恶性肿瘤筛查有重要意义，尤其是对不表达CA 19 -9的PSC患者。这是第一项研究表明，CEA测量和FUT基因分型的联合使用是临床有益的，它可能会提高胆道恶性肿瘤的早期检测在临床实践中。这种方法在筛查其他常见的胃肠道恶性肿瘤时也是有效的。
Background Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden’s index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P = 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies.