Furthermore, it is known that circulating levels of IGFBP-3 and -4 can be affected by multiple, systemic confounding factors, including diet, exercise, pregnancy, growth hormone, and age.[34,35] Therefore, multiple collections will not change the overall conclusion that there is no significant difference in sera levels of either IGFBP-3 or -4 between primary and metastatic melanoma patients. The gene discussed is IGFBP3; the disease is metastatic melanoma.