Table 4.

Studies on cancer related to cocoa or chocolate use, included in this review.

Study	Study Design	Food Type	Main Outcomes
Boutron-Ruault M.C. et al. 1999 [55]	Randomized controlled trial in human	Chocolate	Chocolate intake resulted a risk factor to colorectal tumor development
Carnesecchi S. et al. 2002 [57]	In vitro human study	Cocoa	Cocoa polyphenols interfered with polyamine metabolism, showing an important anti-proliferative effects
Yamagishi M. et al. 2002 [59]	In vitro and in vivo rat study	Cocoa	Cocoa liquor proanthocyanidins inhibited mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rat pancreatic carcinogenesis in the initiation stage, but not mammary carcinogenesis induced by PhIP
Yamagishi M. et al. 2003 [60]	In vivo rat study	Cocoa	Cocoa liquor proanthocyanidins exerted chemopreventive effects in the lung, decreasing the incidence and multiplicity of carcinomas, and the quantitative values of adenomas in a dose-dependent manner in the thyroid
Kenny T. et al. 2004 [61]	In vitro human study	Cocoa	Down-regulation of tyrosine kinase ErbB2 and inhibition of human aortic endothelial cell growth by cocoa procyanidins
Taparia S. & Khanna A. 2016 [62]	In vitro human study	Cocoa	Treatment of ovarian cancer cell lines with cocoa procyanidin-rich extract showed a significant percentage of cells in sub-G1/G0 phase and a significant accumulation of cells in the S phase
Taparia S.S. & Khanna A. 2016 [63]	In vitro human study	Cocoa	Procyanidin-rich extract of natural cocoa powder caused ROS-mediated caspase-3 dependent apoptosis and reduction of pro-MMP-2 in epithelial ovarian carcinoma cell lines
Hong M.Y. et al. 2013 [64]	In vitro rat study	Chocolate	Chocolate diet-fed animals downregulated transcription levels of COX-2 and RelA and lowered the proliferation index
Saadatdoust Z. et al. 2015 [65]	In vitro mice study	Cocoa	Cocoa diet suppresses colitis-associated cancer tumorigenesis