Consumption of Coffee Associated With Reduced Risk of Liver Cancer

A Meta-Analysis

Li-Xuan Sang; Bing Chang; Xiao-Hang Li; Min Jiang

BMC Gastroenterol. 2013;13(34)

Abstract

Background: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer.

Methods: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies.

Results: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I² = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease.

Conclusions: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.

1 2 3 4 5 6

Next Section

Table 1. Quality assessment of case–control studies included in this meta-analysis ¹
Study	Adequate definition of cases	Representativeness of cases	Selection of control	Definition of control	Control for important factor or additional factor²	Exposure assessment	Same method of ascertainment for cases and controls	Nonresponse rate³	Total quality scores
Kuper et al.,¹¹ 2000	★	★	-	★	★	-	★	-	5
Gallus et al.,¹² 2002	★	★	-	★	★	-	★	-	6
Gelatti et al.,¹³ 2005	★	★	-	★	★★	★	★	-	7
Ohfuji et al.,¹⁴ 2006	★	★	-	★	★★	-	★	-	6
Tanaka et al.,¹⁵ 2007	★	★	★	★	★	-	★	-	6
Montella et al.,¹⁶ 2007	★	★	-	★	★★	-	★	-	6
Wakai et al.,¹⁷ 2007	★	★	★	★	★	-	★	-	6
Ohish et al.,¹⁸ 2008	★	★	★	★	★★	-	★	-	7
Leung et al.,¹⁹ 2011	★	★	-	★	-	★	★	-	5

¹A study can be awarded a maximum of one star for each numbered item except for the item Control for most important factor or second important factor.
²A maximum of two stars can be awarded for Control for most important factor or second important factor. Studies that controlled for hepatitis B virus (HBV) or HCV infection received one star, whereas studies that controlled for alcohol drinking received one additional star.
³One star was awarded if there was no significant difference in the response rate between control subjects and cases in the chi-square test (P > 0.05).

Table 2. Quality assessment of cohort studies included in this meta- analysis ¹
Study	Representativeness of the exposed cohort	Selection of the unexposed cohort	Ascertainment of exposure	Outcome of interest not present at start of study	Control for important factor or additional factor²	Outcome assessment	Follow-up long enough for outcomes to occur³	Adequacy of follow-up of cohorts⁴	Total quality scores
Shimazu et al.,²⁰ 2005	★	★	★	★	★★	★	★	★	9
Shimazu et al.,²⁰ 2005	★	★	★	★	★★	★	★	★	9
Inoue et al.,²¹ 2005	-	★	★	★	★	★	★	★	7
Kurozawa et al.,²² 2005	★	★	★	★	★★	★	★	-	8
Hu et al.,²³ 2008	★	★	★	★	★★	★	★	★	9
Inoue et al.,²⁴ 2009	-	★	★	★	★★	★	★	★	8
Johnson et al.,²⁵ 2011	-	★	★	★	★	★	★	★	7

¹A study can be awarded a maximum of one star for each numbered item except for the item Control for most important factor or second important factor.
²A maximum of two stars can be awarded for Control for most important factor or second important factor. Studies that controlled for HBV or HCV infection received one star, whereas studies that controlled for alcohol drinking received one additional star.
³A cohort study with a follow-up time > 7 y was awarded one star.
⁴A cohort study with a follow-up rate > 75% was awarded one star.

Table 3. Characteristics of studies included in the meta-analysis
Author	Design	Study population	Study period and outcome	Case/Control	Coffee consumption	Risk estimate (95% CI)	Covariate adjustments
Kuper et al.,¹¹ 2000	HCCS	Greece	1995–1998 HCC incidence	333/360	Nondrinkers	1	Age, gender, years of schooling, HBsAg and/or anti-HCV status
					<20 cups/week	1.1 (0.5–2.6)
					≥20 cups/week	0.9 (0.4–2.5)
Gallus et al.,¹² 2002	HCCS	Greece Italy	1995–1998	834/1912	Nondrinkers	1.0	Age, sex, smoking, alcohol drinking, history of diabetes or hepatitis, education, BMI
			1984–1997 HCC incidence		1 cup/day	1.2 (0.9–1.6)
					2 cup/day	1.0 (0.7–1.3)
					≥3 cups/day	0.7 (0.5–1.0)
Shimazu et al.²⁰ 2005	CS1	Japan	1984–1992 Primary liver cancer incidence	70/22404	Nondrinkers	1.0	Age, sex, smoking, alcohol drinking, history of liver disease
					occasionally	0.56 (0.33–0.97)
					≥1 cups/day	0.53 (0.28–1.00)
Shimazu et al.,²⁰ 2005	CS2	Japan	1990–1997 Primary liver cancer incidence	47/38703	Nondrinkers	1.0	Age, sex, smoking, alcohol drinking, history of liver disease
					occasionally	1.05 (0.52~2.16)
					≥1 cups/day	0.68 (0.31~1.51)
Kurozawa et al.,²² 2005	CS	Japan	1988–1999 HCC mortality	258/83966	Total	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	Age, sex, smoking, alcohol habits, history of diabetes or liver disease, education
					Nondrinkers	1.0
					<1 cup/day	0.83 (0.54–1.25)
					≥1 cup/day	0.50 (0.31–0.79)
					Men	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Nondrinkers	1.0
					<1 cup/day	0.91(0.57–1.45)
					≥1 cup/day	0.49(0.28–0.85)
					Women	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Nondrinkers	1.0
					<1 cup/day	0.64 (0.27–1.51)
					≥1 cup/day	0.51 (0.20–1.31)
Inoue et al.,²¹ 2005	CS	Japan	1990–2001 HCC incidence	334/90452	Men and women	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	Age, sex, study area, ethanol intake, green vegetable, green tea and smoking
					Almost never	1.0
					1–2 day/week	0.75 (0.56–1.01)
					3–4 day/week	0.79 (0.55–1.14)
					1–2 cups/day	0.52 (0.38–0.73)
					3–4 cups/day	0.48 (0.28–0.83)
					≥5 cups/day	0.24 (0.08–0.77)
					Men	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Almost never	1.0
					1–2 day/week	0.74 (0.52–1.05)
					3–4 day/week	0.76 (0.50–1.16)
					1–2 cups/day	0.55 (0.38–0.80)
					3–4 cups/day	0.41 (0.21–0.77)
					≥5 cups/day	0.27 (0.09–0.87)
					women	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Almost never	1.0
					1–2 day/week	0.77 (0.43–1.37)
					3–4 day/week	0.89 (0.43–1.84)
					1–2 cups/day	0.43 (0.20–0.90)
					3–4 cups/day	0.89 (0.31–2.59)
					≥5 cups/day	-----
Gelatti et al.,¹³ 2005	HCCS	Italy	1994–2003 HCC incidence	250/500	Nondrinkers	1.0	Age, sex, alcohol drinking, HBV and/or HCV infection
					1–2 cups/day	0.8 (0.4–1.3)
					3–4 cups/day	0.4 (0.2–0.8)
					≥5 cups/day	0.3 (0.1–0.7)
Ohfuji et al.,¹⁴ 2006	HCCS	Japan	2001–2002 HCC incidence	73/253	Nondrinkers	1.0	Age, sex, smoking, alcohol drinking, time since first identification of liver disease, BMI, disease severity, family history of liver disease, interferon therapy
					<1 cup/day	0.61 (0.18–2.03)
					≥1 cup/day	0.38 (0.13–1.12)
Tanaka et al.,¹⁵ 2007	PCCS	Japan	2001–2004 HCC incidence	209/1253	Nondrinkers	1.0	Age, sex, smoking status, heavy alcohol drinking,
					occasionally	0.33 (0.22~0.48)
					1–2 cups/day	0.27 (0.15~0.48)
					≥3 cups/day	0.22 (0.11~0.43)
Montella et al.,¹⁶ 2007	HCCS	Italy	1999–2002 HCC incidence	185/412	Abstainers	2.28 (0.99–5.24)	Age, sex, alcohol drinking, HBV and/or HCV infection, education, smoking, alcohol drinking
					<14 cups/week	1.0
					14–20 cups/week	0.54 (0.27–1.07)
					21–27 cups/week	0.57 (0.25–1.32)
					≥28 cups/week	0.43 (0.16–1.13)
Wakai et al.,¹⁷ 2007	NCCS	Japan	1988–1990 HCC incidence	96/3444	Nondrinkers	1.0	Age, sex, smoking, alcohol drinking, consumption of areca,educational levels, ethnicity,source of hospital
					<1 cup/day	0.77 (0.45–1.32)
					≥1 cup/day	0.49 (0.25–0.96)
Hu et al.,²³ 2008	CS	Finland	1997–2002 HCC incidence	128/60323	Total	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	Age, sex, smoking, alcohol drinking, education, study year, diabetes and chronic liver disease BMI and during follow up.
					0–1 cup/day	1.0
					2–3 cups/day	0.66 (0.37–1.16)
					4–5 cups/day	0.44 (0.25–0.77)
					6–7 cups/day	0.38 (0.21–0.69)
					≥8 cups/day	0.32 (0.16~0.62)
					Men	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					0–1 cup/day	1.0
					2–3 cups/day	0.68 (0.35–1.31)
					4–5 cups/day	0.35 (0.18–0.71)
					6–7 cups/day	0.31 (0.15–0.63)
					≥8 cups/day	0.28 (0.13–0.61)
					Women	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					0–1 cup/day	1.0
					2–3 cups/day	0.62 (0.19–2.04)
					4–5 cups/day	0.60 (0.20–1.82)
					6–7 cups/day	0.58 (0.19–1.82)
					≥8 cups/day	0.41 (0.10–1.70)
Ohishi et al.,¹⁸ 2008	NCCS	Japan	1999–2002 HCC incidence	224/644	Nondrinkers	1.0	Hepatitis virus infection, alcohol consumption, smoking habits, BMI, diabetes mellitus, and radiation dose to the liver
Ohishi et al.,¹⁸ 2008	NCCS	Japan	1999–2002 HCC incidence	224/644	Daily	0.40 (0.16–1.02)
Inoue et al.,²⁴ 2009	CS	Japan	1993–1994 HCC incidence	110/18815	Total	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	Age, sex, area, smoking, alcohol drinking, BMI, diabetes mellitus, green tea consumption, serum ALTlevel, and HBV and HCV infection status
					Almost never	1.0
					<1 cup/day	0.67 (0.42–1.07)
					1–2 cups/day	0.49 (0.27–0.91)
					≥3 cups/day	0.54 (0.21–1.39)
					Men	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Almost never	1.0
					<1 cup/day	0.79 (0.46–1.37)
					1–2 cups/day	0.37 (0.17–0.81)
					≥3 cups/day	0.32 (0.10–1.10)
					Women	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
					Almost never	1.0
					<1 cup/day	0.39 (0.15–1.03)
					1–2 cups/day	0.92 (0.36–2.38)
					≥3 cups/day	0.69 (0.11–4.22)
Johnson et al.,²⁵ 2011	CS	Chinese	1993–2006 HCC incidence	362/61321	Nondrinkers	1.0	Age at recruitment, sex, dialect group, year of recruitment, BMI, level of education, consumption of alcoholic beverages, smoking, black tea and green tea intake, and history of diabetes.
					0-<1 drinkers/day	0.94 (0.63–1.40)
					1-<2 drinkers/day	1.17 (0.87–1.56)
					2-<3 drinkers/day	0.78 (0.56–1.07)
					≥3 drinkers/day	0.56 (0.31–1.00)
Leung et al.¹⁹ 2011	HCCS	HongKong	2007–2008 HCC incidence	109/125	<1 time/week	1.0	Age, sex, alcohol drinking, cigarette smoking, tea consumption and physical activity
?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	1–3 times/week	0.58 (0.24–1.36)	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	≥4 times/week	0.41 (0.19–0.89)	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?

ALT: alanine aminotransferase; BMI: body mass index; CI: confidence interval; HbsAg: hepatitis B surface antigen; HCCS: hospital-based case–control study; PCCS: population-based case–control study; NCCS: nested case–control study; CS: cohort study; HCC: hepatocellular carcinoma.

Table 4. Pooled relative risks and 95% CI for coffee consumption and liver cancer risk
Study	No. of studies	No. of cases	Relative risk (95% CI)	Heterogeneity
Study	No. of studies	No. of cases	Relative risk (95% CI)	Q	P	I²(%)
High versus non/almost never intake	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
All studies	16	3,622	0.50 (0.42–0.59)	16.71	0.337	10.2%
Study design	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
Cohort studies	7	1,309	0.48 (0.38–0.62)	2.47	0.676	0.0%
Case–control studies	9	2,313	0.50 (0.40–0.63)	12.38	0.125	36.8%
Study region	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
Asia	11	1,892	0.45 (0.36–0.56)	7.86	0.642	0.0%
Europe	5	1,730	0.57 (0.44–0.75)	7.09	0.131	43.6%
Study gender	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
Male	4	583	0.38 (0.25–0.56)	1.83	0.609	0.0%
Female	4	247	0.60 (0.33–1.10)	0.94	0.815	0.0%
Adjustment for main confounders^a	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?	?dctmLink chronic_id='0901c791801ed00f' object_id='0901c791801ed00f' edit_widget_type=graphic??dctmEditor selectedObject='0901c791801ed00f'?
Adjusted	11	2,512	0.54 (0.46–0.66)	8.5	0.581	0.0%
Unadjusted	5	1,110	0.39 (0.28–0.54)	5.34	0.254	25.1%