In this large population-based prospective cohort study, green tea consumption was inversely associated with overall risk of colorectal cancer (P = 0.06, marginally significant). This inverse association was statistically significant among non-smokers after Bonferroni correction for multiple comparisons. No significant association was found among smokers.
Green tea contains many polyphenolic compounds, mainly catechins, comprising 30–40% of the extractable solids of dried green tea leaves (8
). These compounds, especially epigallocatechin-3-gallate, the major catechin of green tea, have been shown to have many cancer-inhibitory properties in both in vitro
and in vivo
animal studies. These include antioxidative and anti-inflammatory activities (20
), inhibition of the formation of N
-nitroso compounds and heterocyclic amines (potential carcinogens for colorectal cancer) (22
), modulation of xenobiotic metabolizing enzymes (23
), trapping of activated forms of carcinogens (24
) and modulation of signal transduction pathways, which leads to inhibition of cell proliferation and transformation, induction of apoptosis and cell cycle arrest and inhibition of tumor invasion and angiogenesis (8
). Because green tea catechins are not completely absorbed by the gut, catechins can be present in native form at high concentrations in the intestinal lumen (27
). Thus, it has been postulated that the digestive tract may represent a good target for potential chemoprevention with tea because of the high bioavailability of tea catechins in digestive tract organs (7
Green tea is the most commonly consumed tea in Shanghai, accounting for 98.6% of tea consumed by male tea drinkers. The finding of an inverse association between green tea consumption and colorectal cancer risk in our prospective cohort study is consistent with our previous findings from two large case–control studies in Shanghai (28
) as well as another prospective cohort study, the Shanghai Women’s Health Study (SWHS) (30
). In both case–control studies, which involved 1328 and 1805 incident cases of colorectal cancer, respectively, green tea consumption was found to be associated with a reduced risk of colorectal cancer in a dose–response manner (28
). The inverse association was further confirmed in an analysis conducted among participants of the SWHS, a cohort of 74
942 women, 97.3% of whom are non-smokers (30
). Results from other previous case–control studies, mainly conducted in Japan, have been mixed but generally pointed toward an inverse association, with a summary odds ratio of 0.74 (95% CI: 0.63–0.86) (12
). Five cohort study reports on this topic, including our report from the SWHS, have been published to date. Three cohort studies reported an inverse association of green tea consumption with both colon and rectal cancers (30
), colorectal cancer combined (31
) or rectal cancer only (32
); two studies reported a null association (32
); and one study suggested no effect of green tea on colorectal cancer in women, but increased risk for advanced stage cancer in men (34
). A potential effect modification by cigarette smoking on the association was not evaluated in the study (34
). In contrast, we found that green tea consumption was associated with reduced risk for both early-and late-stage colorectal cancers in our earlier report on female non-smokers (30
) and the current study of male non-smokers.
It should be noted that many of the previous studies on tea and colorectal cancer risk were not designed specifically to evaluate the effect of tea, and thus, data on tea consumption were usually not comprehensive (few studies collected information on amount or years of tea consumption) (11
). The lack of heterogeneity of tea consumption in some study populations, e.g. ~95% of study participants drinking tea every day (35
), may have hindered these studies from evaluating the association of cancer risk with green tea consumption. In addition, inadequate controlling for potential confounding or failure to account for effect modifiers may also have contributed to the inconsistency (11
). In particular, the habit of drinking tea often coexists with cigarette smoking and/or alcohol consumption in many populations, which has been found to confer a substantial effect modification on the association between tea consumption and cancer risk (15
). In the present study, consumption of green tea was associated with an overall 23% reduction in risk of colorectal cancer. After accounting for effect modification by cigarette smoking, we found that risk was reduced by 46% among non-smokers, similar to findings observed in our previous study of esophageal cancer (15
). The strong correlation of tea consumption with cigarette smoking, alcohol consumption, physical inactivity and higher intake of red meat may, in part, explain the null association we observed between tea consumption and cancer risk in smokers. It is also possible that the anticancer effect of green tea consumption is visible only in groups with lower risk of colorectal cancer but may not be strong enough to reverse the adverse effects of other concurrent risk factors such as cigarette smoking, as observed in this study.
In this study, a significant dose–response relationship was observed for the amount of green tea consumed (Ptrend
= 0.01) but not for the duration in years of lifetime green tea consumption. However, in our earlier report from the SWHS, we found that the reduction in risk was most evident among women with longer duration of green tea consumption (30
). The median duration of lifetime green tea consumption in women was 16 years, with a 3-fold interquartile range from 8 to 24 years. In the present study, the variation in years of green tea consumption in men was relatively small (interquartile range: 19–32), which may have limited our ability to evaluate the dose–response relationship for lifetime duration of green tea consumption.
Most tea consumed in Western societies is black tea. Frequent consumption of black tea has also been associated with reduced risk for digestive tract cancers in some (36
) but not all studies (12
). In our study, only 743 (1.2%) participants of the SMHS drank black tea regularly and exclusively, which limited our ability to assess the association of black tea with colorectal cancer risk. The association between drinking coffee and colorectal cancer risk has also been evaluated in several previous studies (38
). We did not collect information on coffee consumption since coffee is not a commonly consumed beverage in this population.
The specifics of tea consumption habits vary substantially among and between populations with regard to the types and amounts of tea consumed. In studies of tea and health, the number of cups of tea consumed has been commonly used to assess the amount of exposure. The bioactivity of a cup of tea is affected by many factors, especially the amount of dry tea leaves used for tea preparation (39
). A recent case–control study found a significant reduction in the risk of rectal cancer with increasing intake of black tea measured in grams of dry weight consumed per month (40
). The observed association, however, was substantially diminished when tea consumption was measured in liters of tea consumed. This observation suggests that differences in the methods of assessing tea consumption may have contributed to the conflicting results reported by previous epidemiologic studies. The most common method of green tea preparation in Shanghai is to brew dry green tea leaves with hot water. Higher green tea consumption measured in dry weight has been consistently associated with reduced risk of cancers of the colon and rectum (28
), esophagus (15
), stomach (41
), pancreas (29
) and lungs (16
) in studies conducted in Shanghai.
The current study has several notable strengths. We comprehensively evaluated green tea consumption and colorectal cancer risk by both the amount and duration of green tea consumption. Other strengths of the study include a population-based prospective study design, high participation rates and a virtually complete cohort follow-up, all of which help to minimize many sources of bias inherent in case–control studies. However, as with any observational study, some error in the measurement of tea consumption is likely. Because the exposure assessment was conducted prospectively and prior to cancer diagnosis, it is possible that any measurement error is non-differential by case/control status, which would tend to attenuate the true association between green tea consumption and colorectal cancer risk. In addition, residual confounding may be a potential concern, although we carefully adjusted for a wide range of potential confounding factors, including socioeconomic status and known risk factors for colorectal cancer.
In conclusion, this prospective cohort study among men in Shanghai suggests that regular consumption of green tea may confer protection against colorectal cancer, in particular, for non-smokers. These findings are consistent with data from both in vitro and in vivo experiments, indicating that green tea may serve as an effective chemopreventive agent. With a longer period of follow-up, we should be able to provide a more precise risk estimate according to the duration and amount of tea consumption.