Association between coffee consumption and all‐sites cancer incidence and mortality

The preventive effect of coffee on cancer at different sites has been reported, but the effect on all‐sites cancer incidence has not been extensively investigated. We evaluated the association between frequency of coffee consumption and risk of all‐sites cancer incidence and mortality among 39 685 men and 43 124 women (age 40–79 years, at baseline), in the Three‐Prefecture Cohort Study. The association between frequency of coffee consumption and risk of all‐sites cancer incidence and mortality was assessed by a Cox proportional hazards regression model, adjusted for potential confounders. During 411 341 person‐years among men and 472 433 person‐years among women, a total of 4244 men and 2601 women developed cancer at different sites and a total of 3021 men and 1635 women died of cancer at different sites. We showed an inverse association between frequency of coffee consumption and all‐sites cancer incidence in both men and women. Comparing participants who consumed coffee with those who never drank coffee, the adjusted hazard ratios (95% confidential interval) for all‐sites cancer incidence was 0.74 (0.62–0.88) for coffee consumption of ≥5 cups/day in men (P for trend < 0.001) and 0.76 (0.58–1.02) in women (P for trend = 0.020). Coffee consumption frequency was inversely associated with mortality from all‐sites cancer. In this population, increasing coffee consumption resulted in a decreased risk of all‐sites cancer incidence and mortality.     

Association between green tea/coffee consumption and biliary tract cancer: A population‐based cohort study in Japan

Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population‐based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45–74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person‐years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46–0.97]), and a non‐significant trend of decreased risk associated with increased consumption was observed (P‐trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non‐significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption.     

Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study

Background:

Studies document that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. However, studies on the direct association of magnesium with pancreatic cancer are few and findings are inconclusive. In this study, we aimed to investigate the longitudinal association between magnesium intake and pancreatic cancer incidence in a large prospective cohort study.

Method:

A cohort of 66 806 men and women aged 50–76 years at baseline who participated in the VITamins And Lifestyle (VITAL) study was followed from 2000 to 2008. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatic cancer incidence by magnesium intake categories.

Result:

During an average of 6.8-year follow-up, 151 participants developed pancreatic cancer. Compared with those who met the recommended dietary allowance (RDA) for magnesium intake, the multivariable-adjusted HRs (95% CIs) for pancreatic cancer were 1.42 (0.91, 2.21) for those with magnesium intake in the range of 75–99% RDA and 1.76 (1.04, 2.96) for those with magnesium intake <75% RDA. Every 100 mg per day decrement in magnesium intake was associated with a 24% increase in the incidence of pancreatic cancer (HR: 1.24; 95% CI: 1.02, 1.50; P_trend=0.03). The observed inverse associations appeared not to be appreciably modified by age, gender, body mass index, and non-steroidal anti-inflammatory drug use but appeared to be limited to those taking magnesium supplementation (from multivitamins or individual supplement).

Conclusions:

Findings from this prospective cohort study indicate that magnesium intake may be beneficial in terms of primary prevention of pancreatic cancer.     

A prospective investigation of coffee drinking and endometrial cancer incidence

Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50-71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51-0.80; P(trend) = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86-0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87-0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (P(interaction) = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41-0.72; P(trend) = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.     

Risk of pancreatic cancer in relation to alcohol drinking,coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk

We evaluated the associations of such lifestyle factors as alcohol drinking, coffee consumption and medical history with risk of death from pancreatic cancer in a large-scale prospective cohort study [the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC study)] in Japan. Subjects were 110,792 (46,465 men and 64,327 women) inhabitants who were enrolled from 45 areas throughout Japan. At baseline, a self-administered questionnaire was used to obtain information on lifestyle factors and medical history. Cox proportional hazard models were used to calculate relative risks. During the follow-up period (mean +/- SD 8.1 +/- 1.8 years), 225 deaths due to pancreatic cancer were identified. Overall, neither alcohol nor coffee intake was associated with risk of death from pancreatic cancer. Heavy coffee consumption (> or =4 cups/day), however, may increase the risk. Men who reported a history of diabetes mellitus and women who reported a history of gallstone/cholecystitis were at significantly (2-fold) increased risk of death from pancreatic cancer.     

Prospective study of the relationship between coffee and tea with colorectal cancer risk: The PLCO Cancer Screening Trial

Background:

Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent.

Methods:

A prospective analysis was carried out to examine the relationships of coffee and tea intake with colorectal cancer risk in 57 398 men and women in the intervention arm of the National Cancer Institute-Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a national screening study that limits differential detection biases. Coffee and tea intakes were assessed by food frequency questionnaire.

Results:

Six hundred and eighty-one incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer (relative risk (RR)=1.08, 95% confidence interval (CI)=0.79–1.48, P_trend=0.23). Stratifying by cancer site (P_{heterogeneity}=0.48) or stage (P_{heterogeneity}=0.83) did not alter the relationship. Associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk overall (RR=0.77, 95% CI=0.55–1.09, P_trend=0.17) or by cancer site (P_{heterogeneity}=0.14) or stage (P_{heterogeneity}=0.60). These associations were not modified by several colorectal cancer risk factors.

Conclusion:

The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.     

扬中市1991-2015年肝癌发病及死亡趋势分析

目的 分析江苏省扬中市1991-2015年肝癌发病和死亡的长期时间变化趋势和分布特征.方法 根据1991-2015年江苏省扬中市肝癌发病与死亡登记资料,运用Joinpoint回归模型拟合肝癌发病与死亡趋势,同时运用年龄-时期-出生队列(APC)模型,评估年龄、时期和出生队列对发病和死亡趋势的影响.结果 1991-201...     

Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women

Objective:This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort.Methods:A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996–2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk.Results:We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90–1.17) for total fat, 1.06 (0.93–1.20) for saturated fat, 1.06 (0.93–1.21) for monounsaturated fat, and 1.00 (0.89–1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status.Conclusions:In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.     

Prospective study of breast cancer in relation to coffee,tea and caffeine in Sweden

Studies of coffee and tea consumption and caffeine intake as risk factors for breast cancer are inconclusive. We assessed coffee and tea consumption, caffeine intake, and possible confounding factors among 42,099 women from the Swedish Women's Lifestyle and Health study, the participants of which were aged 30–49 years at enrollment in 1991–1992. Complete follow‐up for breast cancer incidence was performed through 2012 via linkage to national registries. Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer. During follow‐up 1,395 breast cancers were diagnosed. The RR was 0.97 (95% CI 0.94–0.99) for a 1‐unit increase in cups of coffee/day, 1.14 (95% CI 1.05–1.24) for a 1‐unit increase in cups of tea/day, and 0.97 (95% CI 0.95–1.00) for a 100 mg/day increase in caffeine intake. Although the RR for no consumption (RR = 0.86, 95% CI 0.69–1.08), a group with a relatively small number of women, was not statistically significant, women with higher consumption had a decreased breast cancer risk (3–4 cups/day: RR = 0.87, 95% CI 0.76–1.00; ≥5 cups/day: RR = 0.81, 95% CI 0.70–0.94) compared to women consuming 1–2 cups of coffee/day. Compared to no consumption, women consuming >1 cups tea/day showed an increased breast cancer risk (RR = 1.19, 95% CI 1.00–1.42). Similar patterns of estimates were observed for breast cancer risk overall, during pre‐ and postmenopausal years, and for ER+ or PR+ breast cancer, but not for ER? and PR? breast cancer. Our findings suggest that coffee consumption and caffeine intake is negatively associated with the risk of overall and ER+/PR? breast cancer, and tea consumption is positively associated with the risk of overall and ER+/PR+ breast cancer.     

CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer

Cancer risk can be influenced by the exposure to endogenous or environmental toxins. Polymorphic enzymes involved in the metabolic activation/detoxification of carcinogens may account for individual variations of risk. We studied the polymorphisms of five enzymes of the P450 superfamily, CYP1A1, CYP1A2, CYP2D6, CYP2E1 and CY3A4, as risk factors for liver disease progression and cancer in hepatitis C virus-infected patients. CYP genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR. Different stages of disease were considered, as follows: 90 asymptomatic carriers and 87 chronic hepatitis, 92 cirrhosis and 91 hepatocellular carcinoma (HCC) cases. Reference allele frequencies were obtained from 99 blood donors. Allele distributions among categories were compared using the chi(2) test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to express relative risks. Independent associations were modeled by correspondence analysis and logistic regression. Frequencies of the CYP1A1 highly inducible alleles, MspI m2 and Val, were increased in liver disease patients compared with carriers; no specific association with HCC was found. The high-activity CYP2E1 c2 allele was underrepresented among HCC patients with respect to other HCV categories, including cirrhosis. CYP2D6 poor metabolizer (PM) genotypes were significantly more frequent in healthy subjects (7.1%) and carriers (11.1%) than in hepatitis/cirrhosis (4.6%) and HCC (1.2%) patients. This was confirmed by multivariable analysis. PM genotypes protected against progressive disease as ORs reduced proportionally to stage. The age at diagnosis for HCC was anticipated in non-PM individuals. No differences were seen for CYP1A2 and CYP3A4 genes. Polymorphic variants of CYP genes may contribute to the progression of liver disease and HCC risk in HCV-infected subjects.     

Dietary melatonin and liver cancer incidence in Japan: From the Takayama study

There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population-based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population-based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow-up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin-containing foods might play a role in the prevention of liver cancer.     

Magnesium intake and primary liver cancer incidence and mortality in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratio_{tertile 3 vs. 1}: 0.44; 95% confidence interval: 0.24, 0.80; p_trend = 0.0065) and mortality (subdistribution hazard ratio_{tertile 3 vs. 1}: 0.37; 95% confidence interval: 0.19, 0.71; p_trend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all p_nonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.     

Dietary trace element intake and liver cancer risk: Results from two population‐based cohorts in China

Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997–2013) and men (2002–2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case–control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow‐up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35–0.73; p_trend = 0.001). Further adjustment for hepatitis B virus infection in the nested case–control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21–0.69; p_trend < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.     

2012年至2020年重庆地区居民肝癌死亡率及疾病负担变化趋势

目的:了解2012年至2020年重庆地区居民肝癌死亡率及疾病负担变化趋势。方法:肝癌死亡个案病例资料（ICD-10:C22）来源于重庆市全人群死因监测报告数据库。采用SPSS 26.0统计分析死亡率、标化死亡率、早死所致的寿命损失年（years of life lost,YLL）和平均减寿年数（average years of life lost,AYLL）等指标,不同性别与地区间死亡率比较用χ2检验,趋势分析采用年度变化百分比（annual percentage change,APC）表示。结果:2012年重庆市肝癌死亡率与标化死亡率分别为29.87/10万与20.27/10万,2020年重庆市肝癌死亡率与标化死亡率分别为31.21/10万与18.16/10万,死亡率与标化死亡率APC分别为0.39%与-0.83%,变化趋势均无统计学差异（P＞0.05）。2012年至2020年男性历年肝癌死亡率均高于女性,差异均有统计学意义（P＜0.01）。2012年至2020年农村地区历年肝癌死亡率均高于城市,差异均有统计学意义（P＜0.01）。2012年重庆市肝癌导致的YLL率为8.72‰,2020年YLL率为8.02‰,APC为-1.28%,变化趋势无统计学差异（P＞0.05）,AYLL以年均1.66%的速度下降（P＜0.05）。男性AYLL高于女性,分别以年均1.55%（P＜0.05）和1.96%（P＜0.05）的速度下降,城市AYLL低于农村AYLL,城市和农村AYLL总体上分别以年均1.59%（P＜0.05）和1.72%（P＜0.05）的速度下降。结论:重庆市肝癌死亡率较高,早死导致的疾病负担重,男性与农村地区居民是肝癌发生的重点人群。     

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996

Background:

Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected.

Methods:

Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate.

Results:

Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57–62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55–8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52–12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40–9.33) in 1969–1973 to 34.71 (95% CI: 23.10–52.16) in 1992–1996 for those with cirrhosis compared with those without.

Conclusion:

In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.     

Coffee consumption and stomach cancer risk in a cohort of Swedish women

Few prospective studies have examined the relationship between coffee consumption and risk of stomach cancer, and the findings have been inconsistent. We prospectively investigated the association of long-term coffee consumption with risk of stomach cancer in a population-based cohort study of 61,433 Swedish women. Information on coffee consumption was collected with a food-frequency questionnaire at baseline (1987-1990) and updated in 1997. During a mean follow-up of 15.7 years from 1987 through June 2005, 160 incident cases of stomach cancer were diagnosed. Coffee consumption was positively associated with the risk of stomach cancer. Compared to women who consumed 1 or fewer cups of coffee per day, the multivariate hazard ratios were 1.49 (95% = 0.97-2.27) for women who drank 2-3 cups per day and 1.86 (95% CI = 1.07-3.25) for those who drank 4 or more cups per day (p for trend = 0.01). An increase of 1 cup of coffee per day was associated with a statistically significant 22% increased risk of stomach cancer (hazard ratio = 1.22; 95% CI = 1.05-1.42). These prospective data suggest that coffee consumption may increase the risk of stomach cancer in a dose-response manner. This finding needs to be confirmed in other prospective studies.     

Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study

Background:

Patients with chronic lymphocytic leukaemia (CLL) are known to have increased risks of second cancer. The incidence of second cancers after CLL has not been reported in detail for Australia, a country with particularly high levels of ultraviolet radiation (UVR).

Methods:

The study cohort comprised of all people diagnosed with a primary CLL between 1983 and 2005 in Australia. Standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) were calculated using Australian population rates.

Results:

Overall, the risk of any second incident cancer was more than double that of the general population (SIR=2.17, 95% confidence interval (CI)=2.07, 2.27) and remained elevated for at least 9 years after CLL. Risks were increased for many cancers, particularly melanoma (SIR=7.74, 95% CI=6.85, 8.72). The risk of melanoma increased at younger ages, but was constant across >9 years of follow-up. Chronic lymphocytic leukaemia patients also had an increased risk of death because of melanoma (SMR=4.79, 95% CI=3.83, 5.90) and non-melanoma skin cancer (NMSC; SMR=17.0, 95% CI=14.4, 19.8), suggesting that these skin cancers may be more aggressive in CLL patients.

Conclusion:

We speculate that a shared risk factor, such as general immune suppression, modulated by UVR exposure may explain the increased risk of melanoma and NMSC in CLL patients.     

Coffee consumption and the risk of primary liver cancer: pooled analysis of two prospective studies in Japan

Although case-control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self-administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow-up with 170,640 person-years) and Cohort 2 (7 years of follow-up with 284,948 person-years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46-1.09) and 0.58 (0.36-0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high-risk population are needed.