血清胃蛋白酶原作为美国胃癌的生物标志物：一项使用 PLCO 癌症筛查试验数据的巢式病例对照研究。
Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.
机构信息
Montefiore Medical Center/Albert Einstein College of Medicine, Department of Surgery, Bronx, New York.
Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Bronx, New York.
出版信息
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1426-1432. doi: 10.1158/1055-9965.EPI-21-1328.
BACKGROUND
Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer.
METHODS
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 μg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported.
RESULTS
Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%).
CONCLUSIONS
Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer.
IMPACT
PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.
背景
胃癌缺乏特异性症状，导致诊断较晚，死亡率较高。血清胃蛋白酶原是萎缩性胃炎的生物标志物，也是胃癌的前体，可能有助于检测出胃癌风险增加的人群。
方法
前列腺癌、肺癌、结直肠癌和卵巢癌（PLCO）筛查试验于 1993 年至 2001 年在美国进行。对 105 名 PLCO 参与者的预诊断血清样本进行了基于 ELISA 的胃蛋白酶原检测，这些参与者患有胃癌，209 名年龄、性别和种族匹配的对照。胃蛋白酶原阳性（PG+）定义为胃蛋白酶原 I≤70μg/L 和胃蛋白酶原 I/II 比值≤3.0。报告了 PG+对胃癌的条件逻辑回归模型的结果，以及敏感性和特异性。
结果
与对照组相比，胃癌病例在基线时更可能为 PG+（31.4% vs. 5.5%，P<0.001）。与 PG-相比，PG+与胃癌风险增加 8.5 倍相关[95%置信区间（CI）=3.8-19.4]。在调整了幽门螺杆菌、胃癌家族史、教育、吸烟和 BMI 后，这种风险仍然显著（调整后的 OR，10.6；95%CI，4.3-26.2）。在亚组分析中，PG+个体患非贲门胃癌的风险增加了 11 倍（OR，11.1；95%CI，4.3-28.8）；相反，他们患贲门胃癌的风险没有显著增加（OR，2.0；95%CI=0.3-14.2）。PG+状态对非贲门（44.3%；93.6%）和贲门胃癌（5.7%；97.2%）均具有低敏感性但高特异性。
结论
来自大型前瞻性队列研究的预测血清胃蛋白酶原水平与胃癌风险相关，特别是非贲门胃癌。
影响
PG 状态可能识别出患非贲门胃癌风险较高的个体，以便进行有针对性的筛查或干预。见 Zhou 和 Huang 的相关评论，第 1257 页。
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