Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting

• Published in: International journal of cancer 2020-02, Vol.146 (3), p.627-634
• Main Authors: Balavarca, Yesilda, Weigl, Korbinian, Thomsen, Hauke, Brenner, Hermann
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Cancer; Cancer screening; Carcinogenesis; Colonoscopy - statistics & numerical data; Colorectal cancer; Colorectal carcinoma; colorectal neoplasm; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - etiology; Early Detection of Cancer - statistics & numerical data; Environmental risk; Female; Genetic factors; genetic loci; Genetic Loci - genetics; Genetic Predisposition to Disease; Germany - epidemiology; Health risk assessment; Health risks; Humans; Life Style; Male; Medical History Taking; Medical research; Medical screening; Middle Aged; Optimization; Predictive Value of Tests; risk allele; Risk Assessment - methods; Risk Factors; risk score; screening; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32272

Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental‐genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high‐risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study. The performances of single and joint environmental‐genetic scores were evaluated with estimates and 95% confidence intervals (CI) of the absolute risk, relative risk and predictive ability using the area under the curve (AUC). Individuals with higher environmental risk scores showed increasing ACRN risk, with 3.1‐fold for intermediate risk and 4.8‐fold for very high risk, compared to the very low environmental risk group. Similarly, individuals with higher genetic risk scores showed increasing ACRN risk, with 2.2‐fold for intermediate risk and 3.5‐fold for very high risk, compared to the lowest genetic risk group. Moreover, the joint environmental–genetic score improved the ACRN risk stratification and showed higher predictive values (AUC = 0.64; 95%CI = 0.60–0.67) with substantial difference (p = 0.0002) compared to the single environmental score (0.58; 0.55–0.62). The integration of environmental and genetic factors looks promising for improving targeting individuals at high‐risk of colorectal neoplasm. Applications in practical screening programs require optimization with additional genetic and other biomarkers involved in colorectal carcinogenesis. What's new? Risk scores based on either environmental (ERS) or genetic (GRS) factors can facilitate efforts to predict colorectal cancer (CRC) risk. Whether these scores combined would prove more effective for CRC risk prediction is unknown. Here, the utility of joint environmental‐genetic risk scores (ERS‐GRS) for risk stratification of advanced colorectal neoplasm (ACRN) was investigated in screening colonoscopy study participants in Germany. Individually, elevated ERS or GRS was associated with increased ACRN risk. Compared to either risk score alone, however, joint ERS‐GRS showed higher prediction performance, suggesting that the integration of these scores can potentially improve CRC risk stratification and prediction.