Lifestyle-related variables are suggested to play a major role in the development of colorectal cancer (CRC). Within a 3-year follow-up and intervention study with calcium and antioxidants against growth and recurrence of colorectal polyps, supplementary studies were performed in which different aspects of lifestyle were examined. Instead of polypectomy at diagnosis, polyps <9 mm were left in situ in 116 polyp patients (50-76 years, 50% men). After 3 years, all polyps were removed and subjected to histology. Two different sets of control groups were included (all controls were age- and sex-matched and proven to be free of polyps). We applied two different methods in order to assess most exposure variables. Generally, in case-control studies, the validity of the study outcomes is high if they are similar regardless of choice of controls and methods, since bias due to these choices may affect the risk estimates. In contrast, the validity of the study outcomes is low if dependent upon these choices. Our preliminary data support the theory that different factors may be of importance in different stages of the neoplastive formation, and that lifestyle-related factors are likely to play a major role in CRC development.