Table 1.

Summary of the previously developed CRC risk prediction models

Factors included
ModelStudy design and sampleMethodsFamily historyEnvironmental factorsHigh-risk genetic mutationsResidual risk factorsaApplicabilityStrengthsLimitations
Colditz and colleagues (63) Harvard Cancer Risk IndexEstimated parameters from published data and expert opinionScoring for each risk factor based on strengths of associations from the previous logistic regression analysesFDR with colon cancer (yes/no)BMI, screening (FOBT and sigmoidoscopy), aspirin, inflammatory bowel disease, folate, vegetables, alcohol, height, physical activity, estrogen replacement, OC, red meat, fruits, fiber, saturated fat, cigarette smokingNoneNonePredicts 10-y risk of colon cancerEase of useMay not be applicable to rectal cancer risk prediction. Does not consider family history in relatives beyond first degree and is not applicable for people with a high-risk genetic mutation.
Imperiale and colleagues (84)A cross-sectional study of 1,994 asymptomatic individuals aged ≥50 years identified between 1995 and 2001Scoring for each risk factor (method for score undefined)NoneAge, sex, most advanced distal nonmalignant neoplasm (no polyps; hyperplasia; tubular adenoma <1 cm; advanced lesion—tubular adenoma >1 cm, any polyp with villous histology or severe dysplasia or cancer)NoneNoneDetermines the need for screening colonoscopy based on the findings of a flexible sigmoidoscopy. Predicts risk of proximal colon cancer.Improves efficiency of CRC screeningLimited to individuals having a sigmoidoscopy. May not be applicable to people aged younger than 50 y. Is not applicable for people with strong family history or with a high-risk genetic mutation.
Driver and colleagues (80)A prospective cohort of 21,581 men aged 40 to 84 years (Physician's Health Study); followed-up from 1982 to 2004; 485 incident CRC cases.Logistic regressionNoneAge, smoking, alcohol, BMI [diabetes, physical activity, vegetables, cold cereal multivitamins, vitamin C, and vitamin E were considered but not included in the model]NoneNoneProvides CRC risk score. Predicts 20-y risk of CRC for menEase of use. Based on large sampleLimited to males. Is not applicable to people with a strong family history or with a high-risk genetic mutation.
Freedman and colleagues (64)2,263 cases and 2,833 controls of non-Hispanic white men and women aged ≥50 years identified between 1991–1994 (colon) and 1997–2001 (rectal)Logistic regressionFDR with CRC (yes/no), number of FDR with CRC (0, 1, ≥2)Age, sex, sigmoidoscopy and colonoscopy, current leisure time activity, aspirin and NSAIDs, cigarette smoking, vegetables, BMI, and hormone replacementNoneNonePredicts 5-, 10-, and 20-y, and lifetime risk of developing CRC for men and women older than 50 yUser friendly web version available (108) Based on large sampleMay not be applicable to people younger than 50 y. Does not consider family history in relatives beyond first degree. Is not applicable to people with a strong family history or with a high-risk genetic mutation
Wei and colleagues (65)A prospective cohort of 83,767 women aged 30 to 54 years (Nurses' Health Study); follow-up from 1976 to 2004; 701 incident colon cancer cases.Nonlinear Poisson regressionFDR with CRC (yes/no)Age, sigmoidoscopy and colonoscopy, physical activity, aspirin, cigarette smoking, processed meat or red meat, folate, height, BMI, and hormone replacementNoneNonePredicts cumulative risk of colon cancer for women aged 30 to 70 yEase of use. Based on large sampleMay not be applicable to men or to any women aged older than 70 y. Does not consider family history in relatives beyond first degree. Is not applicable to people with a strong family history or with a high-risk genetic mutation. May not be applicable for rectal cancer risk
Ma and colleagues (83)A prospective cohort of 28,115 men aged 40 to 69 years (Japan Public Health Center–based study–Cohort II); followed-up from 1993 to 2005 (mean, 11.0 y); 543 incident CRC cases.Cox proportional hazards modelNone [FDR with CRC (yes/no) was considered, but not included in the model]Age, BMI, physical activity, smoking, alcohol [diabetes was considered but not included in the model]NoneNoneProvides CRC risk score and predicts 10-y risk of CRC for Japanese men.Ease of useMay not be applicable to non-Japanese or to Japanese females. Is not applicable to people with strong family history or with a high-risk genetic mutation
Chen and colleagues (70) MMRproEstimated parameters from published dataBayesian/segregation analysisFDR and SDR: specific relationship to the proband, history of CRC/EC (yes, no), age at diagnosis, MSI status, and MLH1, MSH2, MSH6 mutation statusAge, race/ethnicity,MLH1, MSH2, MSH6NonePredicts probability of carrying MLH1, MSH2, and MSH6 mutations Predicts 5-y and lifetime risk of CRC and ECIncluded specific family history to second-degree. Uses stand-alone software package that is freely availableDoes not consider family history in relatives beyond second degree. May not be applicable to PMS2 mutation carriers. Does not estimate risk of second primary (metachronous) CRC. Is not applicable to MUTYH mutation carriers.
Cleveland Clinic Tool (109)UnreportedUnknownFDR and SDR: specific relationship to the proband, history of CRC and polyps (yes, no), age at diagnosis of CRC (<50, 50–60, ≥60), age at diagnosis of polyps (<60, ≥60)Age (<50, ≥50), sex, ethnicity, weight, height, CRC screening (colonoscopy, sigmoidoscopy, FOBT), fruit and vegetables consumption, smoking, exercise, person history of CRC and polypsNoneNoneProvides CRC risk score (average/medium/high)User friendly web version available (109)Not possible to assess as methods used for development of this tool have not been published. Does not predict cumulative risk over a specified period

Abbreviations: BMI, body mass index; EC, endometrial cancer; FDR, first-degree relative; FOBT, fecal occult blood test; MSI, microsatellite instability of tumor; NSAID, nonsteroidal anti-inflammatory drugs; OC, oral contraceptive; SDR, second-degree relative.

  • aFamilial aggregation that is not explained by known risk factors (including genetic and environmental risk factors shared by family members).