Background. Volunteers enrolled in preventive trials tend to show a different risk profile, compared to the source population. In the SCORE trial of sigmoidoscopy (FS) screening for colorectal cancer (CRC) we enrolled subjects who responded to an interest in screening questionnaire declaring their interest in having FS. Aim. To assess the impact of self-selection in the study of volunteers willing to be screened on the estimates of CRC incidence and mortality and on the generalisability of the results. Methods. We conducted an incidence and mortality follow-up within the cohort of subjects who had been mailed the recruitment questionnaire in 2 centres (Turin and Genova), where information concerning socio-demographic characteristics of all individuals targeted for recruitment was available from the local population registries. We considered in the analysis 3 response groups: 1) non-responders; 2) uninterested responders, including both eligible and non-eligible refusers; 3) interested responders, including subjects allocated to the control group and a sample of non-eligible interested responders. Subjects allocated to the intervention group were excluded, since their CRC risk was reduced as a result of screening. We compared baseline demographics, CRC risk, all-cause and CRC mortality at 11-year follow-up of enrolled volunteers, nonresponders and refusers, using logistic regression and Cox proportional hazards multivariable models Results. Both subjects who volunteered in the trial and those who refused were better educated than non-responders. Men and people younger than 60 were more likely to volunteer among responders. The median follow-up time was 11.2 years both for incidence and for mortality. CRC incidence was 1.83 x 1000 person-years (PY 95%CI:1.76-1.90; 2,677 CRC cases/1,466,838.6 PY); overall mortality was 11.42 x 1000 PY (95% CI: 11.2511.59; 16,794 deaths/ 1,470,840.0 PY); CRC mortality was 0.60 x 1000 PYs (95% CI: 0.560.64; 881 CRC-related deaths/ 1,470,840.0 PY). Interested responders showed a similar CRC risk as non-responders to the recruitment questionnaire, but their CRC mortality was substantially lower: HR:0.70; 95%CI:0.54-0.91. Similarly, CRCmortality was observed when comparing controls enrolled in the SORE trial to non responders to the recruitment questionnaire (HR:0.72; 95%CI:0.53-0.97). All-cause mortality was reduced both among interested responders (HR:0.61; 95%CI:0.57-0.65) and among thosewho refused recruitment (HR:0.81; 95%CI:0.76-0.86). Conclusion. The implementation of a population based FS screening program would result in a similar reduction in CRC incidence, as observed in the SCORE trial, and in a larger impact on CRC mortality. Individual's awareness of CRC risk, as indicated by the positive response to an interest in screening questionnaire, emerged as a determinant of the SES gradient in CRC mortality.
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