From: Polygenic risk prediction models for colorectal cancer: a systematic review
First author, year [ref] | Study design | Study population | Number of study participants | Type of genetic variants used | GRS computation | Non-genetic factors included in the model | AUC (95% CI) of model without SNPs | AUC (95% CI) of SNP-enhanced model | IDI; NRI |
---|---|---|---|---|---|---|---|---|---|
Abe M, 2017 [22] | Case-control | Japanese | Derivation: 558 cases and 1116 controls; Replication: 547 cases and 547 controls. | 11 SNPs (6 derived from GWASs in US/Europeans, 5 identified in GWASs in East Asians) | Unweighted GRS | Â | Â | Derivation study: 0.6392; Replication study: 0.5695 | Â |
Balavarca Y, 2019 [23] | Case-control | German | 236 non-advanced adenomas, 291 advanced CRC; 487 controls | 39 SNPs | Unweighted GRS; Weighted GRS using weights derived from the same study | Gender, age, FH of CRC, smoking, alcohol intake, red meat consumption, use of NSAIDs, previous colonoscopy and polyps history | 0.584 (0.545–0.622) | Unweighted GRS: 0.636 (0.599–0.672); Weighted GRS: 0.616 (0.579–0.654) |  |
Chandler PD, 2018 [24] | Cohort | US | 23,294 individuals, 329 CRC cases | 5 SNPs | Unweighted GRS | Â | Â | Â | Â |
Cho YA, 2019 [25] | Case-control | Korean | 632 cases 1295 controls | 13 SNPs | Unweighted GRS; Weighted GRS using weights derived from the same study | BMI, physical activity, diet, smoking, alcohol consumption. | Â | Â | Â |
de Kort S, 2019 [26] | Case-cohort | Dutch | 1907 CRC cases, 2729 subcohort members | 18 SNPs | Unweighted GRS | Age, BMI, pant size, CRC first degree relative, smoking, nonoccupational physical activity, intake of: alcohol, meat, vegetables, fish, sweets, added sugar, saturated fats and fiber, total energy. | Â | Â | Â |
Dunlop MG, 2013 [27] | Case-control | European descendents | Genotypes alone: 39,266; In combination with other factors: 11,324; External validation case-control sets: 1563 Swedish cases and 1504 controls, 702 Finnish cases and 418 controls. | 10 SNPs | Unweighted GRS | FH of CRC, age, gender. | Â | Â | Â |
Hiraki LT, 2013 [28] | Case-control | European descendants | 10,061 cases and 12,768 controls | 4 SNPs | Unweighted GRS | Age, gender, center, smoking, batch effects, FH of CRC, BMI, NSAIDs use, alcohol use, dietary calcium, folate and red meat intake, sedentary status, hormone replacement therapy when possible and according to the study. | Â | Â | Â |
Hosono S, 2016 [29] | Case-control | Japanese | Derivation set: 558 cases and 1116 controls Replication set: 547 cases and 547 controls | 6 SNPs | Unweighted GRS | Age, smoke, alcohol consumption, folate intake, BMI, FH of CRC, physical activity. | Derivation study: 0.7009; Replication study: 0.5232 | Derivation study: Genetic only risk score: 0.6046; Combined (genetic + traditional): 0.7167; Replication study: Genetic only: AUC 0.6391; Combined (genetic + traditional) AUC 0.6356 | Â |
Hsu L, 2015 [30] | Case-control | European descendants | Training set: 5811 cases and 6302 controls; Validation set: 866 cases and 869 controls. | 27 SNPs | Unweighted GRS; Weighted GRS using weights derived from literature (results not reported) | Age, gender, FH of CRC, history of endoscopic examinations | Men 0.51 (0.48–0.53); Women 0.52 (0.50–0.55) | Men: AUC 0.59 (0.54–0.64); Women: 0.56 (0.51–0.61) |  |
Huyghe JR, 2019 [31] | Case-control | European descendants | 1439 cases and 720 controls | 95 SNPs | Weighted GRS using weights derived from the same study | Â | Â | Â | Â |
Ibáñez-Sanz G, 2017 [32] | Case-control | Spanish | 1336 cases and 2744 controls. | 21 SNPs | Unweighted GRS; Weighted GRS using weights derived from literature and from the same study (results not reported) | Alcohol consumption, BMI, physical activity, red meat and vegetables intake, NSAIDs/aspirin use, FH of CRC | Environmental risk factors and family history: 0.61 (0.59–0.64) | 0.63 (0.60–0.66) |  |
Iwasaki M, 2017 [33] | Case-control | Japanese men | 675 cases and 675 controls | 6 SNPs | Weighted GRS using weights derived from the same study | Age, BMI, alcohol consumption, smoking. | 0.60 | 0.66 | Significant difference in the inclusive model with a GRS compared to the non-genetic model for the IDI (0.0052; 95% CI: 0.0023–0.0081), continuous NRI (0.36; 95% CI: 0.0023–0.71), and NRI (0.26; 95% CI: 0.0039–0.43). |
Jenkins MA, 2019 [34] | Case-control | North American and Australian | 1181 cases and 999 controls | 45 SNPs | Weighted GRS using weights derived from literature | FH of CRC | Â | Â | Â |
Jeon J, 2018 [35] | case-control | European descendants | Training set: 4875 cases and 5291 controls Validation set: 4873 cases and 5299 controls. | 63 SNPs | Weighted GRS using weights derived from the same study | Gender, height, body mass index, education, type 2 diabetes mellitus, smoking status, alcohol consumption, NSAID/aspirin use, regular use of postmenopausal hormones, gender- and study-specific quartiles of smoking pack-years and dietary factors, total-energy, and physical activity | Men: 0.60 (0.59–0.61); Women: 0.60 (0.59–0.61) | Men: 0.63 (0.62–0.64); Women: 0.62 (0.61–0.63) |  |
Jo J, 2012 [36] | Case-control | Korean | 187 cases and 976 controls | 3 SNPs in men, 5 SNPs in women | Unweighted GRS; Weighted GRS using weights derived from the same study | FH of CRC, age. | Conventional risk factors alone, men: 0.692 (0.647–0.732); Conventional risk factors alone, women: 0.603 (0.569–0.637) | Counted GRS plus traditional risk factors, men: 0.729 (0.682–0.767); Weighted GRS plus traditional risk factors, men: 0.719 (0.677–0.761); Counted GRS plus traditional risk factors, women: 0.650 (0.615–0.680); Weighted GRS plus traditional risk factors: 0.646 (0.612–0.674) |  |
Jung KJ, 2015 [37] | Case-cohort | Korean | 173 cases and 1514 controls | 7 SNPs | Unweighted GRS; Weighted GRS using weights derived from the same study | TRS: age, gender, smoking status, fasting serum glucose, FH of CRC | 0.73 (0.69–0.78) | 0.74 (0.70–0.78) | The NRI (95% CI) for a prediction model with GRS compared to the model with TRS alone was 0.17 (− 0.05–0.37) for colorectal cancer, − 0.17 (− 0.33–0.21) for colon cancer, and 0.41 (0.10–0.68) for rectal cancer. |
Jung SY, 2019 [38] | Cohort | European ancestry (women only) | 6539 individuals, 472 cases developed CRC | 54 SNPs | Â | Age and % calories from saturated fatty acid | Â | Â | Â |
Marshall KW, 2010 [39] | Case-control | North American | Training set: 112 CRC and 120 controls. Validation set: 202 CRC and 208 controls (only individuals aged ≥50 years). | 7 genes |  |  |  | Training set: AUC 0.80 (0.74–0.85); Validation set: AUC 0.80 (0.76–0.84) |  |
Prizment AE, 2013 [40] | Cohort | Caucasian | 8657 individuals (205 cases) | 20 SNPs | Weighted GRS using weights derived from literature | Â | Â | Â | Â |
Rodriguez-Broadbent H, 2017 [41] | Case-control | European descendants | 9254 cases and 18,386 controls | 38 SNPs related to total cholesterol circulating levels, 14 SNPs related to triglyceride circulating levels, 9 SNPs related to LDL circulating levels, 43 SNPs related to HDL circulating levels | Â | Â | Â | Â | Â |
Schmit SL, 2019 [42] | Case-control | European descendants | Discovery stage: 36,948 cases and 30,864 controls; Replication set: 12,952 cases and 48,383 controls; Generalizability in East Asians, African Americans, and Hispanics: 12,085 cases and 22,083 controls. | 76 SNPs: 67 previously published SNPs and 9 novel SNPs | Weighted GRS using weights derived from the same study | Â | Â | Â | Â |
Shi Z, 2019 [43] | Case-control | Caucasian | 387 cases and 13,427 controls | 30 SNPs | Weighted GRS using weights derived from literature | Population-standardization | Â | Â | Â |
Smith T, 2018 [44] | Cohort | UK | Taylor model: 361,543 (1623 cases); Wells model: 286,877 (1294 cases) | 41 SNPs | Weighted GRS using weights derived from literature | Taylor model: age-specific CRC rates and estimated RR for different degrees of FH of CRC. Wells model: age, diabetes, multi-vitamin usage, FH of CRC, education, BMI, alcohol use, physical activity, NSAIDs use, red meat intake, smoking and estrogen use (women only). | Taylor model: 0.67 (0.65–0.68); Wells model: 0.68 (0.67–69) | Taylor model:0.69 (0.67–0.70); Wells model: 0.69 (0.65–0.68) |  |
Thrift AP, 2015 [45] | Case-control | European descendants | 10,226 cases and 10,286 controls | 696 SNPs | Weighted GRS using weights derived from literature | Â | Â | Â | Â |
Thrift AP, 2015 [46] | Case-control | European descendants | 10,226 cases and 10,286 controls | 77 SNPs for BMI; 47 SNPs for waist-hip ratio (WHR) | Weighted GRS using weights derived from literature | Â | Â | Â | Â |
Wang HM, 2013 [47] | Case-control | Taiwanese | 218 cases and 385 controls | 16 SNPs in the short model; 26 SNPs in the full model | Â | Â | Â | 16-SNPs model: 0.724; 26-SNPs model: 0.734 | Â |
Wang K, 2018 [48] | Cohort | Chinese | 64 CRC cases (172 digestive cancer cases, 9636 controls) | 9 SNPs |  |  | AFP level: 0.523 (0.456–0.591); CA19–9 level:0.524 (0.451–0.597); CEA level: 0.568 (0.492–0.645); AFP, CA19–9, CEA level: 0.509 (0.439–0.579) | AFP level -genetic corrected: 0.524 (0.458–0.591); CA19–genetic corrected CA19–9 level: 0.525 (0.452–0.597); CEA level-genetic corrected 0.572 (0.495–0.649); AFP, CA19–9, CEA level-genetic: 0.564 (0.487–0.641) |  |
Weigl K, 2018 [49] | Case-control | German | Genotype: 294 advanced neoplasms, 249 non-advanced adenomas, 500 controls Replication: 462 controls, 140 advanced adenomas, 355 non-advanced adenomas | 48 SNPs (replication analyses within the TCPS with a subset of 35 SNPs of the original GRS) | Unweighted GRS; Weighted GRS using weights derived from literature (results not reported) | Gender, age, previous colonoscopy, physical activity, BMI | Model adjusted for age and gender: 0.599; Model adjusted for age, gender, previous colonoscopy, physical activity: 0.607; Model adjusted for age, gender, previous colonoscopy, physical activity, BMI: 0.615 | Model adjusted for age and gender: 0.653; Model adjusted for age, gender, previous colonoscopy, physical activity: 0.658; Model adjusted for age, gender, previous colonoscopy, physical activity, BMI: 0.665 | The NRI and IDI of model including Genetic Risk Score were respectively of 0.29 (0.14–0.43) and 0.04 (0.03–0.05) when the model was adjusted for age and gender; 0.30 (0.15–0.44) and 0.04 (0.03–0.05) when adjusted for age, gender, previous colonoscopy, physical activity and 0.29 (0.14–0.43) and 0.04 (0.03–0.05) when the model was adjusted for age, gender, previous colonoscopy, physical activity, BMI. |
Weigl K, 2018 [50] | Case-control | German | 2363 cases and 2198 controls. | 44 SNPs | Unweighted GRS; Weighted GRS using weights derived from literature (results not reported) | Gender, age, education, previous colonoscopy, smoking, hormone replacement therapy (women only), BMI, FH of CRC | Â | Â | Â |
Xin J, 2018 [51] | Case-control | Chinese | 1316 cases and 2229 controls | 14 SNPs | Unweighted GRS; Weighted GRS using weights derived from literature and from the same study | Smoking status | The highest quartile respect to the lower quartile showed an OR (95%CI) of: 2.70 (2.06–3.54) in the simple count GRS model, 2.74 (2.19–3.43) in the directed logistic regression GRS model, 2.56 (2.05–3.20) in the odds ratio weighted GRS model, 2.90 (2.32–3.63) in the explained variance weighted GRS model, 2.51 (2.01–3.14) in the explained variance weighted OR GRS model. |  | Model were compared among each other respect to NRI (95%CI; p-value) and IDI (95%CI; p-value): the simple-count-GRS vs. logistic regression weighted OR-GRS showed an NRI of − 0.082 (− 0.159, − 0.007; p value: 0.033) and an IDI of − 0.002 (− 0.004, − 2.33E− 04; 0.028); the simple-count-GRS vs. explained variance weighted OR-GRS showed an NRI of 0.017 (− 0.055, 0.090; 0.638) and an IDI of 2.80E− 04 (− 0.001, 0.001; 0.567); logistic regression weighted-GRS vs. explained variance weighted OR-GRS showed an NRI − 0.077 (− 0.153, − 0.001; 0.046) and an IDI of − 5.54E− 04 (− 0.001, − 3.17E− 05; 0.038). In addition, a model including only smoking factors was with a model including smoking factors and simple count GRS (SC-GRS), with an increased AUC, NRI and IDI in combined model of 0.084, 0.317 (0.225, 0.408) and 0.031 (0.023, 0.039) |
Xin J, 2019 [52] | Case-control | Chinese | Chinese studies: 2248 cases and 3173 controls; GECCO study: 4461 cases and 4140 controls | Chinese studies: 19 SNPs vs. 58 SNPs; GECCO study: 19 SNPs vs. 75 SNPs | Weighted GRS using weights derived from the same study | Gender, age, first principal component |  | Chinese studies: 19 SNPs model of 0.597 (0.581–0.613), 58 SNPs model of 0.623 (0.604–0.642); GECCO study: 19 SNPs model of 0.575 (0.563–0.587), 58 SNPs model of 0.585 (0.573–0.597) |  |
Yeh CC, 2007 [53] | Case-control | Taiwanese | 727 cases and 736 controls | 10 SNPs | Â | Age, education, physical activity, coffee consumption, cigarette consumption, alcohol use, staple consumption, meat, vegetable/fruit and fish/shrimp intake. | Â | Â | Â |
Zhang L, 2017 [54] | Case-control | Chinese | 369 cases and 929 controls | 4 SNPs | Â | Age, BMI, physical activity, emotion status, mental stress, cholesterol, drinking and smoking, vegetables and seafood consumption | Â | Â | Â |