Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) and University of Barcelona, Barcelona, Spain.
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1305-1312. doi: 10.1158/1055-9965.EPI-22-0042.
Colorectal cancer has high incidence and associated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario.
We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were genotyped. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated.
Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02-1.06; P < 0.0001]. A 2-fold increase in colorectal cancer risk was observed for subjects in the highest decile of risk alleles (≥65), compared with those in the first decile (≤54; OR = 2.22; 95% CI, 1.59-3.12; P < 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62-0.66].
This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers.
PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers.
结直肠癌在全球范围内发病率和死亡率都很高。建议 50 岁以上的男性和女性进行筛查。像粪便免疫化学检测（FIT）这样的中间筛查方法选择需要进行结肠镜检查的患者，但敏感性不理想。额外的生物标志物可以改善目前的情况。
我们纳入了 2893 名 FIT 检测阳性的个体。如果结肠镜检查后发现结直肠癌高危病变，则将其归类为病例，而对照组则由低危或无病变的个体组成。对 65 种结直肠癌风险遗传变异进行了基因分型。生成了包含性别、年龄、FIT 值和 PRS 的多基因风险评分（PRS）和风险预测的加性模型。
病例组的风险评分高于对照组[每个等位基因的比值比（OR）= 1.04；95%置信区间（CI），1.02-1.06；P < 0.0001]。与风险等位基因最低十分位数（≤54）的个体相比，最高十分位数（≥65）的个体结直肠癌风险增加了两倍（OR = 2.22；95%CI，1.59-3.12；P < 0.0001）。结合性别、年龄、FIT 值和 PRS 的模型在识别高危病变患者方面达到了最高的准确性[交叉验证的 ROC 曲线下面积（AUROC）：0.64；95%CI，0.62-0.66]。
这是首次在两步结直肠癌筛查方案中分析 PRS 的研究。PRS 可以改善当前的结直肠癌筛查，最有可能针对高风险亚组。然而，其能力仅限于预测结直肠癌风险状况，应辅以其他生物标志物。
PRS 具有结直肠癌风险分层的能力，表明其有可能与其他生物标志物一起优化筛查策略。
