Short report
Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a caseecontrol study Winnie Wing-man Leung,1 Suzanne C Ho,1,2 Henry L Y Chan,3 Vincent Wong,3 Winnie Yeo,4 Tony S K Mok4 1
School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, The People’s Republic of China 2 Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong SAR, The People’s Republic of China 3 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, The People’s Republic of China 4 Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, The People’s Republic of China Correspondence to Ms Winnie W Leung, c/o Ms Joyce Leung, 2/F PEC Building, School of Public Health and Primary Care, Prince of Wales Hospital, Shatin, N.T., Hong Kong;
[email protected] Accepted 2 June 2010 Published Online First 6 August 2010
ABSTRACT Background Recent epidemiological studies have reported a dose-dependent protective effect of coffee on hepatocellular carcinoma (HCC) with risk reduction ranging from 30% to 80% in daily coffee drinkers compared with non-drinkers. This study examined whether coffee has a similar protective effect when consumed in moderate quantities in chronic hepatitis B virus (HBV) carriers, a group at high risk of developing liver cancer. Methods A caseecontrol design was employed. 234 HBV chronic carriers (109 cases and 125 controls) were recruited from the Prince of Wales Hospital in Hong Kong from December 2007 to May 2008. Data collection included review of medical records and face-to-face interview. Univariate and multivariate logistic regressions adjusting for age, gender, cigarette smoking, alcohol use, tea consumption and physical activity were conducted with doseeresponse analysis. Results Moderate coffee consumption significantly reduced the risk of HCC by almost half (OR 0.54, 95% CI 0.30 to 0.97) with a significant doseeresponse effect (c2¼5.41, df¼1, p¼0.02), reducing the risk for moderate drinkers by 59% (OR 0.41, 95% CI 0.19 to 0.89). Conclusion The findings provided evidence to support the protective effect of coffee consumption in moderate quantities in HBV chronic carriers.
Liver cancer ranks fourth in incidence and third in mortality among all cancers in Hong Kong.1 Recent epidemiological studies2e14 in Japan and Europe have suggested that coffee drinking lowers the risk of hepatocellular carcinoma (HCC) by 76% in those who consume five or more cups per day,9 with consistent results from meta-analyses.11 12 For hepatitis B virus (HBV) and hepatitis virus C chronic carriers, the protective effect of coffee ranged from 46%14 to 60%4 in daily drinkers. These studies were based on populations with heavy coffee consumption, with per capita consumption of 3.3, 5.3 and 5.5 kg, respectively, for Japanese, Italian and Greek, compared with only 1.1 kg in Hong Kong,15 where only 12% of its residents consume coffee habitually compared with the global average of 55%.16 The question of whether lower coffee consumption would offer the same protection against HCC was potentially important for this population, especially as HBV chronic carrier prevalence and liver cancer incidence rates were high in Hong Kong compared with other parts of the world. We hypothesised that HBV chronic 556
carriers with occasional or moderate coffee consumption were at lower risk of HCC than those with no coffee-drinking habit.
METHODS A caseecontrol study design was employed. All cases and controls were recruited from December 2007 to May 2008 during follow-up appointments at the Special Outpatient Clinic (SOPD) of the Prince of Wales Hospital in Hong Kong. Trained research assistants, blind to the research hypothesis, reviewed the medical record and administered a 15-min face-to-face interview with each participant during follow-up at the SOPD. The study was approved by the Joint CUHK-NTEC Clinical Research Ethics Committee, with informed consents from all participants. Two hundred and thirty-four HBV carriers (109 cases, 125 controls) were entered into the study. Cases and controls were frequency matched by age group and gender distribution. Post-hoc analysis indicated no significant difference in alcohol use (c2¼1.66, df¼1, p¼0.44) and cigarette smoking (c2¼5.44, df¼1, p¼0.07) (table 1). HBV carrier status was defined as the detection of hepatitis B surface antigen in the blood samples of the participant. HCC was defined as the topography code C22.0 (ICD-O-3: C22.0, 817),17 and diagnosis was made based on the medical record for biopsy report, radiological finding of a space-occupying lesion in the liver and a raised a-fetoprotein $400 mg/l, or two coincidental radiological findings of a spaceoccupying lesion in the liver that has characteristic features of HCC. All subjects in the SOPD documented seropositive on hepatitis B surface antigen were eligible for inclusion; those under medication for liver diseases and with a previous history of cancer were excluded to control for confounding due to liver medication and cancer relapse. Exposure to coffee and potential confounders including smoking, alcohol use, tea consumption and physical activity (moderate intensity aerobic exercise) were tapped in terms of intensity (days per week of consumption; and amount per day) and life-time exposure (years of consumption). Univariate logistic regression was performed to examine the crude OR of HCC risk in HBV chronic carriers with a coffee consumption habit compared with those without. Multivariate logistic regression adjusting for potential confounders including age, gender, tea consumption, cigarette smoking, alcohol use and physical activity calculated as the
J Epidemiol Community Health 2011;65:556e558. doi:10.1136/jech.2009.104125
Short report Table 1
Demographic characteristics of cases and controls (N¼234) Cases (N[109) N (%)
Controls (N[125) N (%)
Sex Male Female
86 (78.9) 23 (21.1)
102 (81.6) 23 (18.4)
Age group, years #39 40e49 50e59 $60
5 24 55 25
Cigarette smoking Never smoker Ever smoker Current smoker Alcohol use Never user Ever user Current user
What is already known on this subject c*
df
p Value
0.27
1
0.60
(4.0) (24.8) (50.4) (20.8)
0.36
1
0.95
67 (61.5) 11 (10.1) 31 (28.4)
88 (70.4) 17 (13.6) 20 (16.0)
5.44
1
0.07
69 (63.3) 11 (10.1) 29 (26.6)
89 (71.2) 10 (8.0) 26 (20.8)
1.66
1
0.44
(4.6) (22.0) (50.5) (22.9)
5 31 63 26
2
Recent epidemiological studies reported a dose-dependent protective effect of coffee on HCC with risk reduction ranging from 30% to 80% in daily coffee drinkers compared with nondrinkers.
What this study adds
*c2 test for trend for age group, cigarette smoking and alcohol use.
product of intensity and life-time exposure was performed and compared with the crude OR to examine for confounding. The doseeresponse effect was tested using c2 test for trend, with participants categorised into no coffee-drinking habit (
