喝咖啡对肝癌和胰腺癌风险有不同影响

两项近期发表于《临床胃肠病学与肝病学》(Clinical Gastroenterology and Hepatology)杂志的研究显示，饮用茶、含咖啡因或脱咖啡因咖啡可能对罹患胰腺癌的风险无影响，但摄入任何种类的咖啡可能使肝细胞癌风险降低达50%(取决于摄入量)。

在第一项研究中，荷兰乌德勒支大学医学中心的Nirmala Bhoo-Pathy医生及其合作者对平均11.6年随访期间前瞻性追踪的欧洲10个国家477,312例男、女性中的865例首发胰腺癌病例进行了研究。EPIC(对营养和癌症的欧洲前瞻性研究)队列的参与者于1992年完成基线饮食问卷，然后在2000年末次随访时使用24小时饮食回忆校准。23个参与中心分别位于丹麦、法国、德国、希腊、意大利、荷兰、挪威、西班牙、瑞典和英国，中位咖啡摄入量的范围介于92 ml/d(意大利)至900 ml/d(丹麦)之间。在可获取摄入的所有咖啡类型的参与者(n=269,593)中，半数仅摄入含咖啡因咖啡(50%)，4%仅摄入脱咖啡因咖啡，1/3(34%)摄入上述两种咖啡，12%不饮用咖啡。总队列中的2/3(66%)饮用任何一种类型的茶(含咖啡因茶、绿茶或草本茶)。

结果显示，总的咖啡摄入量［高摄入量与低摄入量相比，风险率(HR)，1.03；95% CI：0.83~1.27］或脱咖啡因咖啡(HR，1.12；95% CI：0.76~1.63)的消耗量(报告为每日、周或月饮用的杯数，然后转化为每日饮用的毫升数)均显示对胰腺癌风险无显著改变。相似的，任何种类的茶消耗量也对胰腺癌风险无影响(HR，1.22；95% CI：0.95~1.56)。当校正一系列混淆因素的影响后或将分析局限于显微镜下可确诊的608例 (70.3%)癌症时，这些风险无改变。混淆因素包括性别、诊所/中心、诊断时的年龄、身高、体重、身体活动、吸烟状态、糖尿病病史、教育水平和能量摄入，包括红肉、加工肉类、酒精、软饮料、茶(对于咖啡的分析)、咖啡(对于茶的分析)以及水果和蔬菜的摄入。对含咖啡因咖啡中度偏低和低摄入量的比较显示，消耗量中度偏低者的风险中度增高(HR，1.33；95% CI：1.02~1.74)，当仅分析显微镜下可确诊的胰腺癌病例时，差异无统计学意义。此外，在任何关于胰腺癌风险的结果中，均未见量效反应。

上述结果支持世界肿瘤研究基金会和美国癌症研究所的观点，即几乎无证据支持咖啡摄入与胰腺癌风险之间存在因果关系(Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.05.029])。

意大利米兰degli Studi di大学的Francesca Bravi 博士研究发现，咖啡摄入量与肝细胞癌风险之间存在量效反应。他的团队在2007荟萃分析的基础上进行了更新，另外纳入4项队列研究和2项病例对照研究，共包括PubMed/MEDLINE中1966~2012年9月期间发表的14篇文章中的8项队列研究和8项 病例对照研究。

结果显示，当按照研究类型分别进行分析时， 3,153例肝细胞癌病例中任何咖啡摄入量导致的总体风险降低40%可分解为：病例对照研究中风险降低44%(RR，0.56；95% CI：0.42~0.75)和队列研究中风险降低36%(RR，0.64；95% CI：0.52~0.78)。在低和高咖啡摄入量与不摄入咖啡的独立比较中，可见量效关系，其中9篇论文中使用每日3杯作为切点，5篇论文中将每日1杯作为切点。低咖啡摄入量使肝细胞癌风险降低了28%(RR，0.72；95% CI：0.61~0.84)，而高消耗量使其风险降低了56%(RR，0.44；95% CI：0.77~0.84)。每日每多喝1杯咖啡导致风险降低20%(RR，0.80； 95% CI：0.77~0.84)。这一结果可分解为：病例对照研究中风险降低23%(RR，0.77；95% CI：0.71~0.83)和队列研究中风险降低17%(RR，0.83；95% CI：0.78~0.88)。对任何咖啡摄入量的风险降低-时间分析显示，2000年的风险降低为20%(RR，0.8；95% CI：0.50~1.29)，至2007年增至41%(RR，0.59；95% CI：0.48~0.72)，在最近的数年间，风险降低稳定保持于40%左右。多数(有意义)的肝癌风险因素对风险率几无影响。这些因素包括乙型和丙型肝炎病毒感染、肝硬化和其他肝脏疾病、社会经济状况、酒精消耗和吸烟。

研究者总结认为，摄入任何种类的咖啡可能使肝细胞癌风险降低达50%，但该研究无法确定饮用咖啡与肝细胞癌之间是否存在因果关系(Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.04.039])。

胰腺癌研究由欧盟和国际肿瘤研究机构资助，多个其他社团、基金会和教育机构对各自国家的队列给予了资助。肝细胞癌研究是由意大利per la Ricerca sul肿瘤协会资助的。两项研究的作者均披露无相关利益冲突。

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By: TARA HAELLE，Internal Medicine News Digital Network

Drinking tea or caffeinated or decaf coffee is unlikely to influence a person’s risk for pancreatic cancer，but consuming coffee of any kind may reduce the risk of the most common liver cancer by as much as 50% (depending on amount consumed)，according to two recent studies in Clinical Gastroenterology and Hepatology.

In the pancreatic cancer study，Dr. Nirmala Bhoo-Pathy of University Medical Center Utrecht，the Netherlands，and her colleagues reported，"Our results strengthen the conclusion made by the World Cancer Research Fund and the American Institute of Cancer Research that there is little evidence to support a causal relation between coffee and risk of pancreatic cancer (Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.05.029]).
 
Meanwhile，a 16-study meta-analysis of coffee intake and risk for hepatocellular carcinoma，which accounts for more than 90% of worldwide liver cancers，revealed a 40% decreased risk (relative risk，0.60; 95% confidence interval: 0.50-0.71) for any coffee consumption vs. no consumption. Yet Dr. Francesca Bravi of Università degli Studi di Milano and her colleagues reported that their findings could not establish a causal relationship between coffee drinking and hepatocellular carcinoma (Clin. Gastroenterol. Hepatol. 2013 [doi:10.1016/j.cgh.2013.04.039]).

Even such a causal relationship may have limited clinical significance，however，considering that more than 90% of primary liver cancers worldwide can theoretically be prevented through hepatitis B vaccination，control of hepatitis C transmission，and reduction of alcohol consumption，Dr. Bravi’s team wrote.

In the first study，Dr. Bhoo-Pathy’s investigation involved inspection of 865 first incidences of pancreatic cancers reported in a cohort of 477,312 men and women from 10 European countries tracked prospectively over a mean 11.6 years of follow-up. The participants in the EPIC (European Prospective Investigation Into Nutrition and Cancer) cohort completed a dietary questionnaire at baseline in 1992，then calibrated with a 24-hour dietary recall by the final follow-up in 2000.

The 23 participating centers were in Denmark，France，Germany，Greece，Italy，the Netherlands，Norway，Spain，Sweden，and the United Kingdom，and median coffee intake across these ranged from 92 ml/day in Italy to 900 ml/day in Denmark. Among the participants with all information on coffee type intake (n = 269,593)，half drank only caffeinated coffee (50%)，4% drank only decaf，a third (34%) drank both，and 12% drank no coffee. Two-thirds (66%) of the total cohort drank tea of any kind (caffeinated，green，or herbal).

Neither total intake of coffee (hazard ratio，1.03; 95% CI：0.83-1.27 for high vs. low intake) nor consumption of decaffeinated coffee (HR，1.12; 95% CI：0.76-1.63) – reported as cups drunk per day，week，or month and then converted to daily milliliters – showed a significant change in pancreatic cancer risk. Tea consumption of any kind similarly had no impact on risk (HR，1.22; 95% CI：0.95-1.56). These risks did not change after accounting for a range of confounders nor when analysis was confined to the 608 (70.3%) cancers that were microscopically confirmed.

Confounders included sex，clinic/center，age at diagnosis，height，weight，physical activity，smoking status，diabetes history，education level，and energy intake，including red meat，processed meat，alcohol，soft drink，tea (for coffee analysis)，coffee (for tea analysis)，and fruit and vegetable intake.

A comparison of moderately low and low caffeinated coffee intake initially revealed a modest increased risk for moderately low consumption (HR，1.33; 95% CI：1.02-1.74) that dropped below statistical significance when only microscopically confirmed pancreatic cancer cases were analyzed. Additionally，no dose-response effect was noted among any of the findings for pancreatic cancer risk.

Yet a dose-response effect was seen in Dr. Bravi’s study investigating coffee consumption and hepatocellular carcinoma risk. Her team’s update of a 2007 meta-analysis included an additional four cohort and two case-control studies，for a total of eight cohort and eight case-control studies from 14 English-language articles included in PubMed/MEDLINE between 1966 and September 2012.

When broken down by study type，the 40% overall risk reduction for any coffee consumption found among 3,153 hepatocellular carcinoma cases split into a 44% reduction in the case-control studies (RR，0.56; 95% CI：0.42-0.75) and a 36% reduction in the cohort studies (RR，0.64; 95% CI：0.52-0.78).

The dose-response relationship was seen in separate comparisons of low and high coffee consumption with no coffee consumption，using three cups a day as the cutoff in nine papers and one cup a day in five papers. Low coffee consumption reduced hepatocellular carcinoma risk by 28% (RR，0.72; 95% CI：0.61-0.84) while high consumption reduced it by 56% (RR，0.44; 95% CI：0.77-0.84).

Each additional cup of coffee per day resulted in a 20% risk reduction (RR，0.80; 95% CI：0.77-0.84). This split into a 23% risk reduction in the case-control studies (RR，0.77; 95% CI：0.71-0.83) and a 17% risk reduction in the cohort studies (RR，0.83; 95% CI：0.78-0.88). A temporal analysis of risk reduction for any coffee consumption showed an increase from 20% risk reduction in 2000 (RR，0.8; 95% CI：0.50-1.29) to 41% in 2007 (RR，0.59; 95% CI：0.48-0.72)，which has remained stable at about 40% the past several years.

Accounting for the most [significant] risk factors for liver cancer had little effect on the risk ratios. These factors included hepatitis B and C infections，cirrhosis，and other liver diseases，socioeconomic status，alcohol consumption，and smoking.

Dr. Bravi’s team suggested that the risk reduction effect could be a real，causal effect arising from antioxidants and other minerals in coffee that may inhibit liver carcinogenesis or from the inverse association between coffee and cirrhosis or coffee and diabetes，both conditions known risk factors for liver cancer. Or，the effect could result，at least in part，from reduced consumption of coffee among patients with cirrhosis or other liver disease.

"Thus，a reduction of coffee consumption in unhealthy subjects cannot be ruled out，although the inverse relation between coffee and liver cancer also was present in subjects with no history of hepatitis/liver disease," the researchers wrote. Yet，they also noted the potentially limited utility of coffee risk reduction given the greater impact on reducing liver cancer risk from hepatitis B vaccination，prevention of hepatitis C，and reduction of alcoholic drinking.

The pancreatic cancer study was funded by the European Commission and the International Agency for Research on Cancer，with a long list of additional societies，foundations，and educational institutions supporting the individual national cohorts. The hepatocellular carcinoma study was funded by a grant from the Associazione Italiana per la Ricerca sul Cancro. The authors in both studies reported no disclosures.