Vitamin D in esophageal cancer: Is there a role for chemoprevention?

Table 1 Studies investigating correlations between vitamin D and esophageal squamous cell dysplasia and carcinoma

Ref.	Study design/location	Vitamin D exposure/status/genetics studies	Statistical correlation
Abnet et al[27]	Cross-sectional study	25-hydroxyvitamin D serum level	RR = 1.86, 95%CI: 1.35-2.62
	China
Chen et al[28]	Prospective study	25-hydroxyvitamin D serum level	ESCC in men:
	China		HR = 1.77, 95%CI: 1.16-2.70
Lipworth et al[29]	Case-control study	Vitamin D dietary intake	ESCC:
	Italy		OR = 0.58, 95%CI: 0.39-0.86
Tran et al[30]	Case-control study	Ultraviolet B radiation	ESCC: No association
	Australia
Wang et al[24]	Case-control study	Genetic polymorphisms	ESCC: No association
	China

ESCC: Esophageal squamous cell carcinoma; OR: Odds ratio; RR: Relative risk; HR: Hazard ratio; CI: Confidence interval.

Table 2 Studies investigating correlations between vitamin D and Barrett’s esophagus or esophageal adenocarcinoma

Ref.	Study design/location	Vitamin D exposure/status/genetics studies	Statistical correlation	Other
Tran et al[30]	Case-control study	Cumulative ambient ultraviolet B radiation	EAC risk: OR = 0.59, 95%CI: 0.35-0.99
	Australia		EAC risk for every 107 J/m2 increase in radiation: OR = 0.82, 95%CI: 0.72-0.93
Mulholland et al[32]	Case-control study	Vitamin D dietary intake via food questionnaire	EAC risk: OR = 1.99, 95%CI: 1.03-3.86
	Ireland		BE risk: no association
Mayne et al[37]	Case-control study	Vitamin D dietary intake	EAC: no association
	United States
Thota et al[38]	Retrospective study of a prospectively collected database	25-hydroxyvitamin D serum levels	EAC: no association
	United States		BE with HGD: no association
Abnet et al[36]	Nested case-control study	25-hydroxyvitamin D serum levels	EAC: no association
	United States, Finland, China
Trowbridge et al[43]	Retrospective study	Vitamin D receptor expression	Not assessed	VDR expression decreased with tumor dedifferentiation
	United States			VDR expression lower in neoadjuvant therapy responders
Trowbridge et al[34]	Retrospective study	Vitamin D receptor expression	Not assessed	VDR expression increased in Barrett’s esophagus
	United States
Zhou et al[35]	Descriptive	Vitamin D receptor expression	Not assessed	VDR expressed in 95% of BE (35/37)
	United States			VDR expressed in 78% of EAC (86/109)
Janmaat et al[25]	Cohort study	Vitamin D receptor polymorphisms	EAC: 2 GT copies:	VDR expression is 2 fold higher in BE as compared to normal esophagus
	Netherlands		OR = 0.50, 95%CI: 0.27-0.96
			BE: 2 GT copies:
			OR = 0.46, 95%CI: 0.26-0.80
Chang et al[45]	Case- control study	Vitamin D receptor polymorphisms	EAC: rs2238139 TT:
	Ireland		OR 0.26, 95% CI: 0.07-0.93
			EAC: rs2107301 TT:
			OR = 0.19, 95%CI: 0.06-0.67
Zgaga et al[5]	Meta-analysis	Ultraviolet B radiation	Vitamin D level and overall esophageal cancer:
	United States	Vitamin D intake	OR = 1.39, 95%CI: 1.03-1.74
		Vitamin D serum levels	Vitamin D intake and EAC:
			OR = 1.45; 95%CI: 0.65-2.24

EAC: Esophageal adenocarcinoma; BE: Barrett’s esophagus; HGD: High-grade dysplasia; VDR: Vitamin D receptor; OR: Odds ratio; CI: Confidence interval.