Confounding effects of hormone replacement therapy in protein biomarker studies

Background: We have recently investigated effects of hormone replacement therapy (HRT) on the serum proteome, and found a high proportion of proteins with altered levels associated with oral estrogen and/or estrogen plus progesterone treatment. Given this finding, we have investigated the extent to which exposure to HRT may have a confounding effect in the assessment of circulating proteins as cancer biomarkers. Methods: We utilize mass spectrometry data collected from the HRT serum proteome studies to estimate the overall effect of postmenopausal hormone therapy on candidate ovarian cancer biomarkers that have been previously reported. Results: Levels of approximately half of the proteins reported as potential ovarian cancer biomarkers were found to be affected by HRT. The impact of HRT on levels of insulin-like growth factor and inhibin protein families was found to be substantial. Conclusions: We conclude that the potential confounding effect of HRT and other types of exposures should be taken into consideration in cancer biomarker study design.