DNC News


Coffee and Cancer: maybe good news

February 26, 2005

Subject: coffee may protect against liver and rectal cancer


Two recent studies about coffee and cancer will be filtering their way down into the news in the next few weeks. At first glance they sound like good news but this skeptical writer still has lingering questions.


Two separate studies, both published in the Feb. 16 issue of The Journal of the National Cancer Institute, examined the impact of coffee drinking on cancer risk.

In one study, researchers in Japan found that regular coffee drinkers had about half the incidence of liver cancer as people who never drank coffee. A second study from the Harvard School of Public Health showed that drinking decaf, but not caffeinated, coffee appeared to have a similar impact on colorectal cancer risk.



In the Harvard study, researchers examined data from two large, ongoing health trials involving 134,000 people. The participants were questioned about their coffee, tea, and caffeine consumption at different time periods over the course of 15 years.

Researcher Karin B. Michels, ScD, and colleagues found no association between consumption of caffeinated coffee or tea and colorectal cancer risk. But people who regularly drank two or more cups of decaffeinated coffee a day had about half the rate of rectal cancer as people who never drank decaffeinated coffee.

Could the apparent protection be explained by the fact that the decaffeinated coffee drinkers tended to have healthier lifestyles than the people who drank caffeinated coffee? Probably not; the tea drinkers in the study also tended to have healthier habits, but had the same cancer risk as people who drank caffeinated coffee. [i]



The second study, reported by researchers from Tokyo 's National Cancer Center , involved 90,500 middle-aged and elderly men and women living in Japan . More than 300 of the participants developed liver cancer during a 10-year period.

The researchers reported that people who drank coffee every day or almost daily had about half the liver cancer risk as those who never drank coffee. The more coffee people drank the lower their risk. And the protective benefits appeared to extend to those with chronic hepatitis C and B infections. They are at very high risk for developing liver cancer. The study did not distinguish between caffeinated and decaffeinated coffee consumption, because few Japanese people drink decaffeinated coffee. [ii]

Liver cancer is common in Japan but relatively rare in the United States , with about 15,000 cases diagnosed annually.

The more coffee people drank the more they seemed to be protected from liver cancer.

It is also interesting that this is a Japanese Study; there's a good chance that the participants in the study not drinking coffee were drinking green tea.


Why am I skeptical? Everyone is quick to justify continuing an activity they consider a vice. That desire may prompt us to jump to conclusions faster than we should. Although there are large numbers of people in these studies, they are still epidemiological. They are not actually testing coffee and the participants were not randomized. Recall all of the studies which said hormone replacement therapy cut heart disease risk in half for menopausal women. Theye were epidemiologic studies similar to this. In the end the studies were proven very wrong.


My first thought when reading through this news was to ask the question, “Almost everyone drinks coffee; what is it about people who don't drink coffee that changes their risk of liver cancer?”


Caffeine is broken down through the Phase I detoxification pathway of the liver. Measuring caffeine clearance from the blood is used in lab tests to assess this portion of liver function. I've written in the past regarding about tamoxifen of the wide genetic variability in liver function. People who avoid coffee may avoid it because of a genetic variation they have that makes them more sensitive to it. In that case the self selected groups in these studies may have different cancer risks based on genetic variability. An Italian group reported in 2003 that the risk of liver cancer in hepatitis C patients varied with the type of phase II liver enzymes they made. [iii] It isn't a great leap to think that phase I liver enzyme variations could also change risk. The coffee may not be the thing making the difference; it may only be the litmus test that hints at underlying genetic variability and variations in body chemistry.


The Japanese study could really be saying coffee drinkers, or fast phase I detoxifiers have less liver cancer. The American study could be saying caffeine avoiders or slow phase I detoxifiers have less rectal cancer.


Skeptic that I am, I'm thinking again about the little stove top espresso maker I saw last week at Cherry Creek, regretting I hadn't bought it now that I know it might be good for me.


A thank you to Milt Hammerly, MD who forwarded these articles to me.





[i] J Natl Cancer Inst. 2005 Feb 16;97(4):282-92.

Coffee, tea, and caffeine consumption and incidence of colon and rectal cancer.

Michels KB, Willett WC, Fuchs CS, Giovannucci E.


Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, and Harvard Medical School, 221 Longwood Ave., Boston, MA 02115, USA. kmichels@rics.bwh.harvard.edu


BACKGROUND: Frequent coffee consumption has been associated with a reduced risk of colorectal cancer in a number of case-control studies. Cohort studies have not revealed such an association but were limited in size. We explored the association between consumption of coffee and tea and the incidence of colorectal cancer in two large prospective cohorts of women and men. METHODS: We used data from the Nurses' Health Study (women) and the Health Professionals' Follow-up Study (men). Consumption of coffee and tea and total caffeine intake were assessed and updated in 1980, 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon or rectum was ascertained through 1998. Hazard ratios were calculated using Cox proportional hazards models that adjusted for potential confounders. All tests of statistical significance were two-sided. RESULTS: During almost 2 million person-years of follow-up, 1438 cases of colorectal cancer were observed. Consumption of caffeinated coffee or tea with caffeine or caffeine intake was not associated with the incidence of colon or rectal cancer in either cohort. For both cohorts combined, the covariate-adjusted hazard ratio for colorectal cancer associated with consumption of each additional cup of caffeinated coffee was 0.99 (95% confidence interval [CI] = 0.96 to 1.03). However, participants who regularly consumed two or more cups of decaffeinated coffee per day had a 52% (95% CI = 19% to 71%) lower incidence of rectal cancer than those who never consumed decaffeinated coffee. CONCLUSIONS: Consumption of caffeinated coffee, tea with caffeine, or caffeine was not associated with incidence of colon of rectal cancer, whereas regular consumption of decaffeinated coffee was associated with a reduced incidence of rectal cancer .


PMID: 15713963 [PubMed - indexed for MEDLINE]




[ii] J Natl Cancer Inst. 2005 Feb 16;97(4):293-300.

Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan .

Inoue M, Yoshimi I, Sobue T, Tsugane S; JPHC Study Group.


Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan. mnminoue@gan2.res.ncc.go.jp


BACKGROUND: An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. METHODS: Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90,452 middle-aged and elderly Japanese subjects (43,109 men and 47,343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. RESULTS: Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for > or =5 cups per day = 0.24 [95% CI = 0.08 to 0.77], P(trend) < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100,000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67 ]). CONCLUSIONS: In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC .


PMID: 15713964 [PubMed - indexed for MEDLINE]



[iii] Int J Cancer. 2003 Apr 10;104(3):310-7

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

Silvestri L, Sonzogni L, De Silvestri A, Gritti C, Foti L, Zavaglia C, Leveri M, Cividini A, Mondelli MU, Civardi E, Silini EM.


Associazione Studi Avanzati Epatiti Virali, Bonate Sotto (BG), Italy .


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. Copyright 2003 Wiley-Liss, Inc.


PMID: 12569554 [PubMed - indexed for MEDLINE]


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