Plasma insulin, IGF‐binding proteins‐1 and ‐2 and risk of colorectal cancer: A prospective study in Northern Sweden

Abstract

Chronically elevated plasma insulin levels have been postulated to increase colon cancer risk, either directly through colonic insulin receptors or indirectly through downregulation of IGFBP‐1 and/or IGFBP‐2, thus increasing IGF activity. Our aim was to examine the relationships of plasma insulin and IGFBPs‐1 and ‐2 with risks of colon and rectal cancers. We conducted a case‐control study nested within the prospective Northern Sweden Health and Disease Cohort. Insulin and IGFBPs were measured in prediagnostic plasma samples from 168 men and women who developed cancers of the colon (n = 110) or rectum (n = 58) and from 336 matched controls. Conditional logistic regression analyses showed no significant relationship of plasma insulin with risk of colon or rectal cancer. In subjects whose blood samples had been collected after more than 4 hr of fasting, insulin showed a moderate but still nonsignificant association with colorectal cancer risk [ORs over quartiles: 1.00, 0.70 (95% CI 0.35–1.39), 1.06 (95% CI 0.55–2.07), 1.63 (95% CI 0.82–3.24); p_trend = 0.10]. Plasma IGFBP‐1 and IGFBP‐2 showed no association with risk of colon and/or rectal cancer, either in the full study population or among the fasting subjects. Our results only moderately support a possible relationship of chronic hyperinsulinemia with colon cancer risk.