Risk factors for neoplastic progression in Barrett’s esophagus

Table 3 Selected published evidence linking adipokines (and ghrelin) with Barrett’s esophagus and progression to esophageal adenocarcinoma

Adipokine	Evidence in BE and EAC
	Relevant study findings	Ref.
Adiponectin (↓ in obesity)	↓ adiponectin receptors in Barrett’s mucosa compared with normal mucosa from controls	Konturek et al[110]
	↑ Bax (pro-apoptotic), ↓ Bcl-2 (anti-apoptotic) and ↑ apoptosis of EAC cell lines on incubation with adiponectin	Konturek et al[110]
	Plasma adiponectin levels inversely associated with BE risk in 50 matched cases (OR 4.7 for each 10 μg/mL ↓ in level) (independent of BMI)	Rubenstein et al[111]
	No difference in adiponectin levels between 51 BE patients and 67 controls	Kendall et al[112]
Leptin (↑ in obesity)	Leptin receptors expressed in esophagus	Francois et al[113]
	↑ proliferation and ↓ apoptosis (via various signalling pathways) in EAC cell lines	Ogunwobi et al[114]
	Leptin levels strongly associated with ↑ risk of BE in males (no association in females)	Kendall et al[112]
	Gastric (fundic) leptin levels positively associated with BE (no association with serum leptin)	Francois et al[113]
Ghrelin (↓ in obesity)	↑ gastric emptying (so may ↓ gastric reflux)	Dornonville et al[115]
	↓ TNF-α-induced COX-2 and interleukin-1-β expression in BE cell line	Konturek et al[110]
	Ghrelin expression negligible in archived EAC cell specimens (vs rich expression in normal mucosa)	Mottershead et al[116]
	↑ serum ghrelin associated with ↓ EAC risk (in overweight subjects)	de Martel et al[117]

BE: Barrett’s esophagus; EAC: Esophageal adenocarcinoma; OR: Odds ratio; BMI: Body mass index; COX-2: Cyclooxygenase-2; TNF: Tumor necrosis factor.