遗传风险评分与结直肠癌筛查人群中晚期肿瘤的患病率相关。
Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population.
机构信息
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
出版信息
Gastroenterology. 2018 Jul;155(1):88-98.e10. doi: 10.1053/j.gastro.2018.03.030. Epub 2018 Mar 21.
BACKGROUND & AIMS: The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population.
METHODS
We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50-79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenoma (NAAs), and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and NAA according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study.
RESULTS
An increased GRS was associated with higher prevalence of advanced neoplasms, but not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence interval [CI], 0.76-1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70-1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8-27.3).
CONCLUSIONS
In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.
背景与目的
特定单核苷酸多态性（SNP）的存在可用于计算个体患结直肠癌（CRC）的风险，称为遗传风险评分（GRS）。我们研究了 GRS 是否可以在筛查结肠镜人群中识别出具有临床相关肿瘤的个体。
方法
我们基于在全面文献检索中发现的与 CRC 相关的 48 个 SNP 推导了 GRS。我们从德国一项筛查结肠镜研究的 1043 名参与者（50-79 岁）中获得了遗传数据，这些参与者于 2005 年至 2013 年期间招募（294 名患有晚期肿瘤，249 名患有非晚期腺瘤（NAA），500 名无肿瘤）。通过聚合其风险等位基因（0、1 或 2），为每位参与者分配一个 GRS。通过多元逻辑回归计算 GRS 下高级肿瘤和 NAA 的风险。计算了风险推进期。我们使用田纳西州结直肠息肉研究的一个子集的数据复制了我们的发现。
结果
GRS 升高与晚期肿瘤的患病率较高相关，但与 NAA 无关。与低 GRS 组相比，GRS 中值和高值组的高级肿瘤风险分别增加了 2.2 倍和 2.7 倍。中 GRS 组的调整后比值比（OR）为 1.09（95%置信区间[CI]，0.76-1.57），NAA 为 1.05（95% CI，0.70-1.55）在高 GRS 组中。对于中 GRS 组的近端高级肿瘤，OR 最大（OR，3.55；95%CI，1.85-6.82），上 GRS 组（OR，3.61；95%CI，1.84-7.10）。中 GRS 与低 GRS 的风险推进期为 13.4 年（95%CI 4.8-22.0），高 GRS 与低 GRS 的风险推进期为 17.5 年（95%CI，7.8-27.3）。
结论
在德国 CRC 筛查研究的遗传分析中，GRS（基于与 CRC 相关的 SNP）增加与高级肿瘤的患病率增加相关。这些发现可用于定义风险适应的筛查年龄。
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