http://www.who.int/mediacentre/factsheets/fs297/en/
http://www.euro.who.int/en/what-we-do/health-topics/noncommunicable-diseases/cancer

J. Ferlay, D.M. Parkin, E. Steliarova-Foucher (2010). Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer ;46(4):765–81.

Up-to-date statistics on cancer occurrence and outcome are essential for the planning and evaluation of programmes for cancer control. Since the relevant information for 2008 is not generally available as yet, we used statistical models to estimate incidence and mortality data for 25 cancers in 40 European countries (grouped and individually) in 2008. The calculations are based on published data. If not collected, national rates were estimated from national mortality data and incidence and mortality data provided by local cancer registries of the same or neighbouring country. The estimated 2008 rates were applied to the corresponding country population estimates for 2008 to obtain an estimate of the numbers of cancer cases and deaths in Europe in 2008. There were an estimated 3.2 million new cases of cancer and 1.7 million deaths from cancer in 2008. The most common cancers were colorectal cancers (436,000 cases, 13.6% of the total), breast cancer (421,000, 13.1%), lung cancer (391,000, 12.2%) and prostate cancer (382,000, 11.9%). The most common causes of death from cancer were lung cancer (342,000 deaths, 19.9% of the total), colorectal cancer (212,000 deaths, 12.3%), breast cancer (129,000, 7.5%) and stomach cancer (117,000, 6.8%).

http://globocan.iarc.fr/factsheets/cancers/all.asp

Stocks P (1970). Cancer mortality in relation to national consumption of cigarettes, solid fuel, tea, and coffee. Br J Cancer; 24: 215–225.

Comparison between the age-adjusted death rates in 1964-65 from cancers of different sites and the annual consumption of cigarettes, solid fuel, tea and coffee as measured by trade statistics in 20 countries reveals the existence of significant correlations.

Cigarette consumption per adult in the population is positively related with lung and bladder cancer in males and insignificantly with lung in females. Negative relations are indicated with the liver and biliary passages, prostate and uterus.
Solid fuel is positively related with the intestine, lung and bladder in both sexes, with leukaemia in males and with breast in females. Nagative associations are indicated with the stomach.

Tea is positively related with intestine except rectum in both sexes and with larynx, lung and breast in females. Negative associations are indicated with the stomach in both sexes and with uterus and leukaemia in females.

Coffee is positively related with the pancreas, prostate and leukaemia in males and with ovary and leukaemia in females.
Specially noteworthy were the contrasts between the intestine and stomach in their associations with solid fuel, cigarettes and tea for which a possible explanation has been suggested.

Arab L (2010). Epidemiologic evidence on coffee and cancer. Nutr Cancer;62:271-83.

Coffee consumption is a major and frequent dietary exposure in diverse cultures around the globe whose safety has been questioned. A substantial body of epidemiologic evidence, consisting of over 500 papers relating the consumption of coffee to cancer of various sites, has accumulated to date. Numerous individual, site-specific meta analyses have been undertaken at various times. However, there is no comprehensive, up-to-date overview of the entirety of the knowledge base. To address this need, this review summarized the findings of the meta analyses and recent papers on site-specific human cancers among coffee consumers. For hepatocellular and endometrial cancers, there appears to be a strong and consistent protective association; for colorectal cancer, the direction of association is borderline protective. There appears to be no association with breast, pancreatic, kidney, ovarian, prostate, or gastric cancer. Risk of bladder cancer appears to be associated with heavy coffee consumption in some populations and among men. The associations with childhood leukemia and mother’s consumption of coffee were ambiguous-with some suggestion of risk at high levels of daily consumption.

http://www.euro.who.int/en/what-we-do/health-topics/noncommunicable-diseases/cancer

Nkondjock A (2009). Coffee consumption and the risk of cancer: an overview. Cancer Lett. ;277:121-5.

Habitual coffee drinking has been associated with a reduced risk of mortality and chronic diseases, including cancer. The favourable influence of coffee is supported by several plausible mechanisms due to the presence of a variety of biological compounds such as caffeine, diterpenes, caffeic acid, polyphenols as well as volatile aroma and heterocyclic substances. Current evidence suggests that coffee consumption is associated with a reduced risk of liver, kidney, and to a lesser extent, premenopausal breast and colorectal cancers, while it is unrelated to prostate, pancreas and ovary cancers. Coffee drinking may still help reduce death due to liver cancer.

http://www.dietandcancerreport.org

Background
Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence.

Available from: http://www.dietandcancerreport.org/

Yu X, et al (2011). Coffee consumption and risk of cancers: a meta-analysis of cohort studies. BMC Cancer, published online ahead of print. DOI:10.1186/1471-2407-11-96.

Background
Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence.

Methods
We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to frequency of coffee intake. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with 1 cup/day increment of coffee consumption.

Results
59 studies, consisting of 40 independent cohorts, met the inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR of cancer was 0.87 (95% CI, 0.82-0.92) for regular coffee drinkers, 0.89 (0.84-0.93) for low to moderate coffee drinkers, and 0.82 (0.74-0.89) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers (RR, 0.97; 95% CI, 0.96-0.98). In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers.

Conclusions
Findings from this meta-analysis suggest that coffee consumption may reduce the total cancer incidence and it also has an inverse association with some type of cancers.

Tamakoshi A, et al (2011). Effect of coffee consumption on all-cause and total cancer mortality: findings from the JACC study. Eur J Epidemiol; 26(4): 285-293.

Coffee consumption is known to be related to various health conditions. Recently, its antioxidant effects have been suggested to be associated with all-cause or cancer mortality by various cohort studies. However, there has been only one small Asian cohort study that has assessed this association. Thus, we tried to assess the association of coffee with all-cause and total cancer mortality by conducting a large-scale cohort study in Japan. A total of 97,753 Japanese men and women aged 40-79 years were followed for 16 years. Hazard ratios and 95% confidence intervals of all-cause and total cancer mortality in relation to coffee consumption were calculated from proportional-hazards regression models. A total of 19,532 deaths occurred during the follow-up period; 34.8% of these deaths were caused by cancer. The all-cause mortality risk decreased with increasing coffee consumption in both men and women, with a risk elevation at the highest coffee consumption level (≥4 cups/day) compared with the 2nd highest consumption level in women, although the number of subjects evaluated at this level was small. No association was found between coffee consumption and total cancer mortality among men, whereas a weak inverse association was found among women. The present cohort study among the Japanese population suggested that there are beneficial effects of coffee on all-cause mortality among both men and women. Furthermore, the results showed that coffee consumption might not be associated with an increased risk of total cancer mortality.

Tverdal A, et al (2011). Coffee intake and oral-oesophageal cancer: follow-up of 389,624 Norwegian men and women 40 – 45 years. British Journal of Cancer; 105(1): 157–161.

Background
The evidence on the relationship between coffee intake and cancer of the oral cavity and oesophagus is conflicting and few follow-up studies have been done.

Methods
A total of 389624 men and women 40–45 years who participated in a national survey programme were followed with respect to cancer for an average of 14.4 years by linkage to the Cancer Registry of Norway. Coffee consumption at baseline was reported as a categorical variable (0 or <1 cup, 1–4, 5–8, 9+ cups per day). Results
Altogether 450 squamous oral or oesophageal cancers were registered during follow-up. The adjusted hazard ratios with 1–4 cups per day as reference were 1.01 (95% confidence interval: 0.70, 1.47), 1.16 (0.93, 1.45) and 0.96 (0.71, 1.14) for 0 or <1 cup, 5–8 and 9+ cups per day, respectively. Stratification by sex, type of coffee, smoking status and dividing the end point into oral and oesophageal cancers gave heterogeneous and non-significant estimates. Conclusion
This study does not support an inverse relationship between coffee intake and incidence of cancer in the mouth or oesophagus, but cannot exclude a weak inverse relationship.

Botelho F, et al (2006). Coffee and gastric cancer: systematic review and meta-analysis. Cad Saude Publica. ;22:889–900.

We systematically reviewed the literature on the association between coffee consumption and gastric cancer and performed a meta-analysis of the results. Published cohort and case-control studies were identified in PubMed and reference lists. Random effects meta-analysis was used to pool effects from 23 studies, and heterogeneity was explored by stratification and meta-regression. The odds ratio (OR) for the overall association between coffee and gastric cancer (highest vs. lowest category of exposure) was 0.97 (95%CI: 0.86-1.09), similar for cohort (OR = 1.02; 95%CI: 0.76-1.37) and case-control studies (population-based: OR = 0.90; 95%CI: 0.70-1.15; hospital-based: OR = 0.97; 95%CI: 0.83-1.13). The OR was 1.26 (95%CI: 1.02-1.57) when considering five studies conducted in the USA, 0.97 (95%CI: 0.82-1.14) for the five Japanese studies, 0.98 (95%CI: 0.81-1.17) for the six studies from Europe, and 0.64 (95%CI: 0.47-0.86) for the two studies from South America. In this meta-analysis we found no adverse effect of coffee associated with gastric cancer. Knowledge on the level of exposure to different coffee constituents may provide a deeper understanding of this reassuring result and the real role of coffee on cancer risk.

Botelho F, et al (2006). Coffee and gastric cancer: systematic review and meta-analysis. Cad Saude Publica. ;22:889–900.

Background
Data of epidemiological studies on the relation between coffee drinking and upper aerodigestive tract cancer risk are scattered and inconclusive. We therefore conducted systematic meta-analyses of observational studies published before October 2009.

Materials and methods
We combined relative risks (RR) with 95% confidence intervals (CI) for cancers of the oral cavity/pharynx (OP) and larynx, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), comparing the highest versus the lowest categories of coffee consumption, using random-effects models.

Results
For OP cancer, the pooled RR was 0.64 (95% CI 0.51–0.80) for highest versus lowest coffee drinking, based on a total of 2633 cases from one cohort and eight case–control studies, with no significant heterogeneity across studies. The RRs were 0.61 (95% CI 0.41–0.89) for European, 0.58 (95% CI 0.36–0.94) for American and 0.74 (95% CI 0.48–1.15) for Asian studies, where coffee consumption is lower. The corresponding RRs were 1.56 (95% CI 0.60–4.02) for laryngeal cancer (732 cases from three case–control studies), 0.87 (95% CI 0.65–1.17) for ESCC (2115 cases from one cohort and six case–control studies) and 1.18 (95% CI 0.81–1.71) for EAC (415 cases from three case–control studies).

Conclusion
Coffee drinking is inversely related to OP cancer risk, while there is no relation with laryngeal cancer, ESCC and EAC.

Bravi F, et al (2007). Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatology. 46:430-5.

Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case-control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for case-control studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case-control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. CONCLUSION: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion.

Leung WW, et al (2011). Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: a case-control study. J Epidemiol Community Health; 65: 556-558.

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 case–control 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 dose–response 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 dose–response effect (χ2=5.41, df=1, p=0.02), 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.

Freedman ND, et al (2009). Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 50:1360-9.

Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment. Participants were followed for 3.8 years for clinical outcomes and, for those without cirrhosis, a 2-point increase in Ishak fibrosis score on protocol biopsies. At baseline, higher coffee consumption was associated with less severe steatosis on biopsy, lower serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, alpha-fetoprotein, insulin, and homeostatic model assessment (HOMA2) score, and higher albumin (P < 0.05 for all). Two hundred thirty patients had outcomes. Outcome rates declined with increasing coffee intake: 11.1/100 person-years for none, 12.1 for less than 1 cup/day, 8.2 for 1 to fewer than 3 cups/day, and 6.3 for 3 or more cups/day (P-trend = 0.0011). Relative risks (95% confidence intervals) were 1.11 (0.76-1.61) for less than 1 cup/day; 0.70 (0.48-1.02) for 1 to fewer than 3 cups/day; and 0.47 (0.27-0.85) for 3 or more cups/day (P-trend = 0.0003) versus not drinking. Risk estimates did not vary by treatment assignment or cirrhosis status at baseline. Tea intake was not associated with outcomes. CONCLUSION: In a large prospective study of participants with advanced hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression.

Luo J, et al (2007). Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study). Eur J Cancer Prev;16:542–8.

Pancreatic cancer is one of the most aggressive and treatment-refractory malignancies in humans. The most effective means of reducing pancreatic cancer mortality may be primary prevention. Although laboratory studies have demonstrated that green tea possesses anticancer activities, results from epidemiological studies have failed to show a consistent cancer-preventive effect. In addition, there is a lingering concern that coffee mighty increase the risk of pancreatic cancer although the most recent epidemiological studies showed no overall association between coffee and risk. Here, we examined the association between the drinking of green tea or coffee and the risk of pancreatic cancer in a large population-based cohort study in Japan (JPHC study). In total, 102 137 participants were followed for an average of 11 years through to the end of 2003. A total of 233 incident cases of pancreatic cancer were identified among 1 116 945 person-years of follow-up. Overall, the risk of pancreatic cancer was not associated with either green tea or coffee intake in our population, although a reduced risk was apparent among men who drank at least three cups of coffee per day compared with those who did not drink any or only rarely drank coffee. In conclusion, our findings support the idea that green tea or coffee consumption does not have a substantial impact on pancreatic cancer risk in general.

Dong J et al. (2011). Coffee drinking and pancreatic cancer risk: a meta-analysis, World Journal of Gastroenterology, 17(9):1204-10.

Aim
To quantitatively assess the relationship between coffee consumption and incidence of pancreatic cancer in a meta-analysis of cohort studies.

Methods
We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Studies were included if they reported relative risks (RRs) and corresponding 95% CIs of pancreatic cancer with respect to frequency of coffee intake. We performed random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of pancreatic cancer associated with a 1 cup/d increment in coffee consumption.

Results
Fourteen studies met the inclusion criteria, which included 671 080 individuals (1496 cancer events) with an average follow-up of 14.9 years. Compared with individuals who did not drink or seldom drank coffee per day, the pooled RR of pancreatic cancer was 0.82 (95% CI: 0.69-0.95) for regular coffee drinkers, 0.86 (0.76-0.96) for low to moderate coffee drinkers, and 0.68 (0.51-0.84) for high drinkers. In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of pancreatic cancer in men, while this association was not seen in women. These associations were also similar in studies from North America, Europe, and the Asia-Pacific region.

Conclusion
Findings from this meta-analysis suggest that there is an inverse relationship between coffee drinking and risk of pancreatic cancer.

Turati F, et al (2011). A meta-analysis of coffee consumption and pancreatic cancer, Annals of Oncology, published online ahead of print. DOI: 10.1093/annonc/mdr3

Background
Since when in 1981 a case–control study showed a positive association between coffee and pancreatic cancer, several studies reported inconsistent results on this issue.

Materials and methods
We conducted a systematic bibliography search updated March 2011 to identify observational studies providing quantitative estimates for pancreatic cancer risk in relation to coffee consumption. We used a meta-analytic approach to estimate overall relative risk (RR) and 95% confidence interval (CI) for the highest versus the lowest coffee consumption categories, using random-effects models.

Results
Based on 37 case–control and 17 cohort studies (10 594 cases), the pooled RR for the highest versus lowest intake was 1.13 (95% CI 0.99–1.29). Considering only the smoking-adjusting studies, the pooled RRs were 1.10 (95% CI 0.92–1.31) for the 22 case–control, 1.04 (95% CI 0.80–1.36) for the 15 cohort, and 1.08 (95% CI 0.94–1.25) for all studies. The pooled RR for the increment of one cup of coffee per day was 1.03 (95% CI 0.99–1.06) for the 28 smoking-adjusting studies reporting three or more coffee consumption categories. No significant heterogeneity was observed across strata of study design, sex, geographic region, and other selected characteristics.

Conclusions
This meta-analysis provides quantitative evidence that coffee consumption is not appreciably related to pancreatic cancer risk, even at high intakes.

Turati F, et al (2011). Coffee, decaffeinated coffee, tea, and pancreatic cancer risk: a pooled-analysis of two Italian case-control studies. Eur J Cancer Prevention; 20(4):287–292.

To evaluate the association between coffee, decaffeinated coffee, and tea consumption and pancreatic cancer risk in a pooled analysis of two Italian case-control studies, between 1983 and 2008, we conducted two case-control studies in Northern Italy, including a total of 688 pancreatic cancer cases and 2204 hospital controls with acute, non-neoplastic diseases. We computed multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for coffee drinking (mostly espresso and mocha), adjusting for age, sex, center, year of interview, education, body mass index, tobacco smoking, alcohol drinking, and diabetes. Compared with coffee nondrinkers, the multivariate OR for coffee drinkers was 1.34 (95% CI: 1.01-1.77). However, there was no trend in risk with respect to dose and duration. The OR for an increment of one cup per day was 1.05 (95% CI: 0.98-1.11). There was no heterogeneity in strata of age, sex, and other covariates, including tobacco smoking. No association emerged for decaffeinated coffee (for drinkers the OR was 0.87, 95% CI: 0.60-1.26, compared with decaffeinated coffee nondrinkers) or tea (for tea drinkers the OR was 0.92, 95% CI: 0.75-1.14). The lack of relationship with dose and duration weighs against a causal association between coffee and pancreatic cancer, which is in agreement with most evidence on the issue.

Tavani A, et al (2004). Coffee, decaffeinated coffee, tea, and cancer of the colon and rectum: a review of epidemiological studies 1990–2003. Cancer Causes Control;15:743–57.

The literature from 1990 to 2003 on the relation between coffee, decaffeinated coffee, tea and colorectal cancer risk has been reviewed. For the relation with coffee, three cohort (517 total cases) and nine case-control studies (7555 cases) analysed colon cancer; three cohort (307 cases) and four case-control studies (2704 cases) rectal cancer; six case-control studies (854 cases) colorectal cancer. For colon cancer most case-control studies found risk estimates below unity; the results are less clear for cohort studies. No relation emerged for rectal cancer. A meta-analysis, including five cohort and twelve case-control studies, reported a pooled relative risk of 0.76 (significant). Any methodological artefact is unlikely to account for the consistent inverse association in different countries and settings. Plausible biological explanations include coffee-related reductions of cholesterol, bile acids and neutral sterol secretion in the colon; antimutagenic properties of selected coffee components; increased colonic motility. Decaffeinated coffee was not related to either colon or rectal cancer in three case-control studies. No overall association between tea and either colon or rectal cancer risk emerged in seven cohort (1756 total cases of colon, 759 of rectal and 60 of colorectal cancer) and 12 case-control studies (8058 cases of colon, 4865 of rectal, 604 of colorectal cancer).

Giovannucci E (1998). Meta-analysis of coffee consumption and risk of colorectal cancer. Am J Epidemiol ; 147: 1043–52.

Several studies have found that coffee consumption is related to a lower risk of colorectal cancer, but results have not been consistent. Thus, a meta-analysis of the published articles was conducted to examine this relation. Because of the various ways data were collected and analyzed, a ‘semiquantitative’ approach that compared the high versus the low category of intake for each study was used. The combined results from 12 case-control studies showed an inverse association between coffee consumption and risk of colorectal cancer (pooled relative risk (estimated by odds ratio) for high vs. low category of coffee consumption (RR) = 0.72, 95% confidence interval (Cl) 0.61–0.84); the findings were similar in population-based and hospital-based case-control studies. Five cohort studies did not support an association (pooled RR = 0.97, 95% Cl 0.73–1.29). The combined results of all studies were driven largely by the case-control studies, which comprised 85 percent of the cases (RR = 0.76, 95% Cl 0.66–0.89). The lower risk of colorectal cancer among substantial coffee drinkers was observed in studies from Asia, Northern and Southern Europe, and North America. The results of this meta-analysis indicate a lower risk of colorectal cancer associated with substantial consumption of coffee, but they are inconclusive because of inconsistencies between case-control and prospective studies, the lack of control for important covariates in many of the studies, and the possibility that individuals at high risk of colorectal cancer avoid coffee consumption. Several ongoing prospective cohort studies, based on extensive dietary questionnaires, may provide important new data to evaluate this hypothesis.

Galeone C, et al (2010). Coffee consumption and risk of colorectal cancer: a meta-analysis of case–control studies. Cancer Causes Control;21:1949-59.

A meta-analysis of case-control studies on coffee consumption and colorectal cancer risk was conducted. Twenty-four eligible studies published before May 2010 were identified, including a total of 14,846 cases of colorectal, colon or rectal cancer. Compared to non/occasional drinkers, the odds ratios (OR) for drinkers were 0.83 (95% CI 0.73-0.95) for colorectal, 0.93 (95% CI 0.81-1.07) for colon and 0.98 (95% CI 0.85-1.13) for rectal cancer, with significant heterogeneity among studies; the corresponding ORs for the increment of 1 cup/day were 0.94 (95% CI 0.91-0.98), 0.95 (95% CI 0.92-0.98), and 0.97 (95% CI 0.95-0.99). For the highest coffee drinkers, the ORs were 0.70 (95% CI 0.60-0.81) for colorectal cancer, 0.75 (95% CI 0.64-0.88) for colon cancer and 0.87 (95% CI 0.75-1.00) for rectal cancer, when compared to non/low drinkers. The results of this meta-analysis of case-control studies suggest a moderate favorable effect of coffee consumption on colorectal cancer risk. The reduced risk was consistent across study design (hospital vs. population based), geographic area, and various confounding factors considered. It may reflect a real protection but also partly or largely be due to reverse causation, i.e. decreased coffee consumption among cases following the onset of bowel symptoms.

Oba S, et al (2006). The relationship between the consumption of meat, fat, and coffee and the risk of colon cancer: a prospective study in Japan. Cancer Lett;244:260-7.

The risk of the development of colon cancer in relation to a western diet was studied in a community-based cohort in Japan. From 1992 to 2000, 13,894 men and 16,327 women were followed. In men, high consumption of processed meat increased the risk in comparison with low consumption (adjusted RR=1.98, 95% CI: 1.24-3.16). In women, daily coffee drinkers had a reduced risk in comparison with individuals who never or rarely drank coffee (adjusted RR=0.43, 95% CI: 0.22-0.85). The findings suggest the possible linkage between a western diet and risk of colon cancer.

Lee KJ, et al (2007). Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and women. Int J Cancer;121:1312-8

We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population-based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population-based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow-up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19-1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women.

Kang NJ. et al (2011). Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis; 32 (6):921-928.

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.

Pelucchi C, et al (2008). Coffee and alcohol consumption and bladder cancer. Scand J Urol Nephrol;42 (Suppl 218):37-44.

Epidemiological studies on coffee, alcohol and bladder cancer risk published up to 2007 were reviewed. Coffee drinkers have a moderately higher relative risk of bladder cancer compared to non-drinkers. The association may partly be due to residual confounding by smoking or dietary factors, but the interpretation remains open to discussion, although the absence of dose and duration-risk relations weighs against the presence of a causal association. Most studies of alcohol and bladder cancer found no association, with some studies finding a direct and other an inverse one. This again may be due to differential confounding effect of tobacco smoking–the major risk factor for bladder cancer–in various populations. Thus, epidemiological findings on the relation between alcohol drinking and bladder cancer exclude any meaningful association.

Lee JE, et al (2007). Intakes of coffee, tea, milk, soda, and juice and renal cell cancer in a pooled analysis of 13 prospective studies. Int J Cancer; 121 : 2246–53.

Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; pvalue, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer.

Montella M, et al (2009). Coffee, decaffeinated coffee, tea intake, and risk of renal cell cancer. Nutr Cancer;61:76-80.

The relation between coffee, decaffeinated coffee, and tea intake and renal cell carcinoma (RCC) risk was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident histologically confirmed RCC and controls were 1,534 patients in hospital for acute non neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex, and age. Coffee intake (mostly espresso and mocha) was not associated with RCC risk, with an OR of 1.02 (95% CI 0.73-1.43) in drinkers of > or = 4 cups/day compared with drinkers of < 1 cup/day. The corresponding ORs were 1.34 (95% CI 0.87-2.07) in men and 0.67 (95% CI 0.38-1.18) in women, 1.91 (95% CI 0.85-4.31) in current smokers and 0.74 (95% CI 0.41-1.31) in never smokers, with no trend in risk with dose. No relation was observed with decaffeinated coffee (OR = 1.38, 95% CI 0.94-2.03 for drinkers compared with nondrinkers) and tea intake (OR = 0.78, 95% CI 0.59-1.05 for drinkers of > or = 1 cup/day compared with nondrinkers). No significant heterogeneity was found for coffee intake across strata of age, education, body mass index, and consumption of sugar. This study, based on a large dataset, provides further evidence that coffee, decaffeinated coffee, and tea consumption are not related to RCC risk.

Park CH, et al. Coffee consumption and risk of prostate cancer: a meta-analysis of epidemiological studies. BJU Int. 2010;106:762-9.
Objective

To evaluate the association between coffee consumption and the risk of prostate cancer.

Methods
We searched PubMed, EMBASE, and the bibliographies of relevant articles in August 2009. Two evaluators independently reviewed and selected articles based on predetermined selection criteria.

Results
Twelve epidemiological studies (eight case-control studies and four cohort studies) were included in the final analysis. In a meta-analysis of all included studies, when compared with the lowest level of coffeeconsumption, the overall relative risk (RR) of prostate cancer for the highest level of coffee consumption was 1.16 (95% confidence interval [CI] 1.01-1.33). In subgroup meta-analyses by study design, there was a significant positive (harmful) association between coffee consumption and prostate cancer risk in seven case-control studies using both crude and adjusted data (RR 1.20, 95% CI 1.02-1.40; and RR 1.21, 95% CI 1.03-1.43, respectively), whereas there was no significant association in four cohort studies using crude or adjusted data (RR 0.97, 95% CI 0.68-1.38; and RR 1.06, 95% CI 0.83-1.35, respectively).

Conclusion
Given that a cohort study gives a higher level of evidence than a case-control study, there is no evidence to support a harmful effect of coffee consumption on prostate cancer risk. Further prospective cohort studies are required.

Wilson KM, et al (2011). Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst; 103(11):876-84.

Background
Coffee contains many biologically active compounds, including caffeine and phenolic acids, that have potent antioxidant activity and can affect glucose metabolism and sex hormone levels. Because of these biological activities, coffee may be associated with a reduced risk of prostate cancer.

Methods
We conducted a prospective analysis of 47,911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter. From 1986 to 2006, 5035 patients with prostate cancer were identified, including 642 patients with lethal prostate cancers, defined as fatal or metastatic. We used Cox proportional hazards models to assess the association between coffee and prostate cancer, adjusting for potential confounding by smoking, obesity, and other variables. All P values were from two-sided tests.

Results
The average intake of coffee in 1986 was 1.9 cups per day. Men who consumed six or more cups per day had a lower adjusted relative risk for overall prostate cancer compared with nondrinkers (RR = 0.82, 95% confidence interval [CI] = 0.68 to 0.98, P(trend) = .10). The association was stronger for lethal prostate cancer (consumers of more than six cups of coffee per day: RR = 0.40, 95% CI = 0.22 to 0.75, P(trend) = .03). Coffee consumption was not associated with the risk of nonadvanced or low-grade cancers and was only weakly inversely associated with high-grade cancer. The inverse association with lethal cancer was similar for regular and decaffeinated coffee(each one cup per day increment: RR = 0.94, 95% CI = 0.88 to 1.01, P = .08 for regular coffee and RR = 0.91, 95% CI = 0.83 to 1.00, P = .05 for decaffeinated coffee). The age-adjusted incidence rates for men who had the highest (≥6 cups per day) and lowest (no coffee) coffee consumption were 425 and 519 total prostate cancers, respectively, per 100 000 person-years and 34 and 79 lethal prostate cancers, respectively, per 100 000 person-years.

Conclusions
We observed a strong inverse association between coffee consumption and risk of lethal prostate cancer. The association appears to be related to non-caffeine components of coffee.

Fagherazzi G, et al (2011). No association between coffee, tea or caffeine consumption and breast cancer risk in a prospective study. Public Health Nutrition; 14(7):1315-1320.

Objective
Numerous mechanisms for the effects of coffee, tea and caffeine on the risk of breast cancer have been suggested. Caffeine intake has already been associated with high plasma levels of female hormones, but associations have not been clearly demonstrated in epidemiological studies.

Design
We examined prospectively the association of coffee, tea and caffeine consumption with breast cancer risk in a French cohort study.

Setting
Dietary information was obtained from a 208-item diet history questionnaire self-administered in 1993-1995. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios and 95 % confidence intervals.

Subjects
The study was conducted on 67 703 women with available dietary information. During a median follow-up of 11 years, 2868 breast cancer cases were diagnosed.

Results
Median intake was 280 ml/d (2·2 cups/d) for coffee and 214 ml/d (1·7 cups/d) for tea. Median caffeine intake was 164 mg/d. No association was found between consumption of coffee, tea or caffeine and breast cancer risk. Sub-analyses by tumour receptor status, menopausal status, type of coffee (regular or decaffeinated) and meals at which beverages were drunk led to the same conclusion.

Conclusions
Results from this prospective study showed no relationship between coffee, tea or caffeine intake and breast cancer risk overall or by hormone receptor status.

Tang N, et al (2009). Coffee consumption and risk of breast cancer: a meta-analysis. Am J Obstet Gynecol;200:290.e1-9.

Objective
This metaanalysis was conducted to assess the association between coffee consumption and breast cancer risk.

Study Design
Relevant studies were identified by searching Medline (1966-May 2008) and the reference lists of retrieved articles. The summary relative risk (RR) with 95% confidence interval (CI) was calculated using a random-effects model.

Results
Nine cohort and 9 case-control studies met the inclusion criteria. The combined RR showed a borderline significant influence of highest coffee consumption (RR, 0.95; 95% CI, 0.90-1.00) or an increment of 2 cups/day ofcoffee consumption (RR, 0.98; 95% CI, 0.96-1.00) on the risk of breast cancer. In stratified analysis, borderline significant associations were observed among cohort and case-control studies and studies conducted in Europe and the United States. However, no significant association was noted among studies conducted in Asia.

Conclusion
Our findings suggest a possible influence of high coffee consumption or an increased coffee consumption on the risk of breast cancer.

Bhoo Pathy N, et al (2010). Coffee and tea intake and risk of breast cancer. Breast Cancer Res Treat.;121:461-7.

Known risk factors account for about 10-15% of breast cancer incidence suggesting that lifestyle exposures are crucial in its etiology. Previous epidemiological studies on the association between coffee and tea consumption and breast cancer risk have been inconsistent. We investigated the association of coffee and tea consumption with the risk of breast cancer among women in EPIC-NL cohort, a population-based prospective cohort in Netherlands with 27,323 participants. Exposure was measured by a validated food frequency questionnaire, and the outcome was verified by direct linkage with the Netherlands Cancer Registry. A total of 681 invasive primary breast cancers were diagnosed in 9.6 years of follow-up. Coffee intake increased the risk of breast cancer by more than twofold as compared to non-consumers (HR; 2.25, 95% CI; 1.30-3.90). This association did not hold after multivariate adjustment which resulted in a HR of 1.17, 95% CI; 0.65-2.12. After adjustment to breast cancer risk factors and lifestyle, no association was observed between intake of coffee or tea and risk of breast cancer across all categories of intake. These results were also not altered by body mass index (BMI). Coffee and tea consumption does not seem to be related to the risk of breast cancer in women.

Li J et al (2011). Coffee Consumption modifies risk of estrogen-receptor negative breast cancer. Breast Cancer Res; 14;13(3):R49.

Introduction
Breast cancer is a complex disease and may be sub-divided into hormone-responsive (estrogen receptor (ER) positive) and non-hormone-responsive subtypes (ER-negative). Some evidence suggests that heterogeneity exists in the associations between coffee consumption and breast cancer risk, according to different estrogen receptor subtypes. We assessed the association between coffee consumption and postmenopausal breast cancer risk in a large population-based study (2,818 cases and 3,111 controls), overall, and stratified by ER tumour subtypes.

Methods
Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated using the multivariate logistic regression models fitted to examine breast cancer risk in a stratified case-control analysis. Heterogeneity among ER subtypes was evaluated in a case-only analysis, by fitting binary logistic regression models, treating ER status as a dependent variable, with coffee consumption included as a covariate.

Results
In the Swedish study, coffee consumption was associated with a modest decrease in overall breast cancer risk in the age-adjusted model (OR> 5 cups/day compared to OR≤ 1 cup/day: 0.80, 95% CI: 0.64, 0.99, P trend = 0.028). In the stratified case-control analyses, a significant reduction in the risk of ER-negative breast cancer was observed in heavy coffee drinkers (OR> 5 cups/day compared to OR≤ 1 cup/day : 0.43, 95% CI: 0.25, 0.72, P trend = 0.0003) in a multivariate-adjusted model. The breast cancer risk reduction associated with higher coffee consumption was significantly higher for ER-negative compared to ER-positive tumours (P heterogeneity (age-adjusted) = 0.004).

Conclusions
A high daily intake of coffee was found to be associated with a statistically significant decrease in ER-negative breast cancer among postmenopausal women.

Nkondjock A, et al (2006). Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Cancer;118:103–7.

Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffeeconsumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1-3, 4-5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72-1.12), 0.75 (95% CI 0.47-1.19) and 0.31 (95% CI 0.13-0.71; p-trend = 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk.
Copyright 2005 Wiley-Liss, Inc.

Kotsopoulos J, et al (2007). The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev;16:912–6.

We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations.

Steevens J, et al (2007). Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis. Br J Cancer; 97 : 1291–4.

In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.

Bravi F, et al (2009). Coffee drinking and endometrial cancer risk: a metaanalysis of observational studies. Am J Obstet Gynecol;200:130-5.

We conducted a metaanalysis of published studies on the relation between coffee drinking and endometrial cancer risk, which included 2 cohort (201 cases) and 7 case-control studies (2409 cases). The summary relative risk (RR) for coffee drinkers vs nondrinkers was 0.80 (95% confidence interval [CI], 0.68-0.94), with significant heterogeneity between studies. Compared with nondrinkers, the summary RR was 0.87 (95% CI, 0.78-0.97) for low-to-moderatecoffee drinkers and 0.64 (95% CI, 0.48-0.86) for heavy coffee drinkers. The summary RR for an increase of 1 cup/d was 0.93 (95% CI, 0.89-0.97), which suggests an inverse relation between coffee and endometrial cancer. However, the causality must be confirmed.