Does the GH-IGF axis play a role in cancer pathogenesis?

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Case-controlled studies show elevated serum insulin-like growth factor-I (IGF-I) in prostate and breast cancer patients.
• Growth hormone (GH) increases IGF-I, raising concerns about its role in cancer initiation.
• Epidemiological studies suggest an association but do not establish causality for IGF-I and cancer risk.

Purpose of the Study:

• To investigate the role of GH and its related factors in cancer initiation.
• To evaluate alternative explanations for elevated IGF-I in cancer patients.
• To assess the impact of GH therapy on cancer risk, considering IGF-I and IGFBP-3 levels.

Main Methods:

• Review of epidemiological studies and human/animal models.
• Analysis of the relationship between IGF-I, IGFBP-3, and cancer risk.
• Examination of data from acromegaly patients and GH transgenic mice.
• Consideration of in vitro studies on IGFBP-3's effects on cancer cells.

Main Results:

• Elevated IGF-I in cancer patients may be due to ascertainment bias, tumor origin, or nutritional factors, not necessarily GH.
• Acromegaly patients and GH transgenic mice show no significant increase in major cancer incidence.
• IGFBP-3 inhibits IGF action and induces apoptosis; GH increases both IGF-I and IGFBP-3.
• Cancer risk appears elevated when high IGF-I coincides with low IGFBP-3.

Conclusions:

• Current data do not support GH as a direct cancer initiation factor.
• GH therapy may not increase cancer risk due to simultaneous increases in IGF-I and IGFBP-3.
• Long-term studies are needed to fully assess GH therapy's cancer risk, considering duration and IGFBP-3 levels.
• Routine monitoring of IGF-I and IGFBP-3 in GH recipients is recommended, but no change in current management is warranted.