The relationship between diabetes mellitus and the risk of colorectal cancer was investigated in a multicenter case-control study, conducted in Italy between 1992 and 1996 on 1225 cases of incident, histologically confirmed colon cancer, 728 cases of rectal cancer, and 4154 controls, who were in the hospital for acute, nonneoplastic diseases. Overall, 66 (5.4%) cases of colon cancer, 50 (6.9%) cases of rectal cancer, and 185 (4.4%) controls reported a history of diabetes. The corresponding multivariate odds ratios (ORs) were 1.2 [95% confidence interval (CI), 0.8-1.6] for colon, 1.5 (95% CI, 1.1-2.2) for rectal, and 1.3 (95% CI, 1.0-1.6) for all colorectal cancers. No association was observed for subjects who were diagnosed with diabetes at ages of < 40 years (7 cases and 27 controls, OR = 0.9). The OR was 1.4 (95% CI, 1.1-1.7) for subjects who were diagnosed with diabetes at ages of > or = 40 years and were likely to have non-insulin-dependent diabetes. The association was also stronger (OR = 1.6; 95% CI, 1.1-2.3) among subjects whose diabetes was diagnosed 10 or more years in advance and who were > or = 60 years old at the time of colorectal cancer diagnosis. None of the other covariates, including sex, education, body mass index, physical activity, energy intake, alcohol drinking, and fiber intake, showed any appreciable modifying effect. Thus, this uniquely large case-control study of colorectal cancer confirms that subjects with non-insulin-dependent diabetes mellitus have a slightly increased risk of colorectal cancer. More importantly, allowance for a large number of identified potential confounding factors, including body mass index, diet, and physical activity, could not explain the excess colorectal cancer risk among subjects with diabetes mellitus. These findings have plausible biological correlations because insulin-like-growth factor-I is a promoter of colon tumor cell growth in vitro.

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