Table 2. Associations of insulin and insulin-like growth factor system components (in serum or plasma) with risk for three major cancers.

Elevated insulin	↑ Colon cancer risk Refs. 138-143	↑ Breast cancer risk (pre-menopausal) Ref. 144	↑ Breast cancer risk (post-menopausal) Refs. 4, 138, 145	↑ Hepatocellular carcinoma risk Refs. 107, 146-148
Elevated IGF-I	↑ Colon cancer risk Refs. 139, 141, 149, 150
IGFBP-1	↓ Colon cancer risk Refs. 139, 141, 142
IGFBP-2	↓ Colon cancer risk Refs. 139, 142

Only those endocrine factors that exhibited a statistically significant and consistent (i.e., over multiple studies) association with specific cancer risk are shown. Some studies reported significant associations of serum IGF-I, IGFBP-1, IGFBP-2 and/or IGFBP-3 with pre-menopausal or post-menopausal breast cancer risk, however a comparable number of other studies reported a lack of such associations.

The liver is the major tissue source of circulating IGF-I and IGFBPs. The relationships of serum IGF-I and IGFBPs with hepatocellular carcinoma risk (and status) are complex, due to the dys-regulated expression of these genes in pre-neoplastic, transformed or cancerous liver cells.