In this large-scale, population-based cohort study conducted among Chinese women in Shanghai, we found no evidence of an association between meat or fat consumption, including any of their subtypes, and colorectal cancer incidence. We also found no apparent association of total fish consumption with colorectal cancer, although intake of cholesterol-rich fish, including eel, shrimp, and shellfish, was related to a higher risk of colon cancer. In addition, we found that colon cancer risk was positively associated with high intake of eggs and cholesterol. Traditional Chinese cooking methods were unrelated to the risk of colorectal cancer with exception of use of smoking as a cooking method, which was related to increased risk of colon cancer.
Meat consumption has long been suspected as an important risk factor for colorectal cancer. This hypothesis was initially based on migrant studies, secular trends of cancer incidence within countries, and international correlations between per capita food disappearance data and incidence rates for the disease [37
]. The geographic distribution of colorectal cancer follows the division between Westernized versus developing countries, and incidence rates are increasing in countries adopting Western-style dietary habits [38
]. Mortality from colon cancer has rapidly increased in the past few decades in Japan, and the increase has generally been ascribed to the Westernization of the diet, characterized by high intake of fat and meat [39
]. Two recent population-based cohort studies conducted in Japan [12
], however, failed to find a positive association between meat intake and incidence of colorectal cancer. The incidence of colorectal cancer in Shanghai has also been increasing during the last two decades [3
]. We found no apparent evidence of a positive association between total meat intake and colorectal cancer risk in this population, similar to results from Japanese studies [12
]. The lack of an overall association between total meat intake and colorectal cancer has also been reported in several cohort studies conducted in European and North American countries [6
]. However, a number of other studies have reported a positive associations ranging from 80 to 120g/day for the highest quintile of meat intake [6
]. The median of raw red meat intake among women in Shanghai is 42.3g/day (1.5 oz/day), which is much lower than the 100g or less per day (3.5 oz/day) of raw red meat recommended by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) [5
]. The average amount of red meat intake for women in countries that participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study ranged from 34.6g/day (1.2 oz/day, Greece) to 81.2g/day (2.9 oz/day, Netherlands), and the mode was 71.3g/day (2.5 oz/day) [7
]. When we analyzed the effect of red meat intake on CRC risk with 80g/day as the reference group, the proportional hazard ratio (HR) was 1.03 (95CI%: 0.73-1.47). When we used 90g/day as the reference, the HR was 1.29 (95CI%: 0.88-1.89) and with 100g/day as the reference, the HR was 1.67 (95CI%: 1.11-2.52). Thus, lack of an association between total meat intake and CRC risk in our study population may be explained by an overall low level of meat consumption.
Several prospective studies have reported an inverse association between colon cancer risk and high intake of poultry and fish [7
]. However, other studies have found that poultry and fish intake were either not associated with risk [9
] or were related to increased risk [18
]. In our study, poultry and total fish intake, including marine and fresh water fish, was unrelated to the risk of colorectal cancer, comparable to results from a study in Japan [30
] where fish intake was high. However, in our study intakes of eel, shrimp and shellfish, all of which have a relatively high level of cholesterol compared to other types of fish, were associated with an increased the risk of colorectal cancer, although some of the associations were only marginally significant. The inconsistency between our findings and results from previous studies that found a protective effect of fish intake on CRC [7
] could be attributed to the effect of water pollution. Nakata et al. [48
] reported a high concentration of DDT in spiny-head croaker, trident goby, and pike eel collected from Hangzhou Bay, south of Shanghai. Fish, particularly shellfish raised in industrial areas such as Shanghai, may have a high level of methyl mercury, polychlorinated dibenzo-p-dioxins and dibenzofurans, organochlorine residues, and other chemicals, some of which have been shown to be mutagens or animal carcinogens [49
]. A few epidemiological studies have also suggested some of these chemicals may be related to colorectal cancer [50
]. Given that the fish intake of women in this population (50.6g/day) is about 1.5 times higher than that of women in European countries (average 32.8g/day) [7
] and that the amount of fresh water fish intake has increased continuously, while salt water fish intake has decreased in the population of Shanghai since 1990 [52
], the effect of long-term consumption of fish, particularly shellfish, on health needs to be further evaluated.
On the other hand, eel, shrimp and shellfish are rich in cholesterol. We found that high intake of eggs, another cholesterol-rich food, and total dietary cholesterol, were positively associated with CRC risk. A combined analysis of 13 case-control studies showed a significant association between dietary cholesterol intake and cancer risk [53
], although prospective studies have, in general, reported null results [19
]. However, a recent prospective study, with a considerably longer follow-up period (up to 32 years) than other prospective studies, suggested that high dietary intake of cholesterol was associated with increased risk of colorectal cancer [18
]. Cholesterol acts as a co-carcinogen in the development of colorectal cancer in animal studies [54
]. Several other mechanisms have also been proposed to explain the effect of dietary cholesterol in modifying the carcinogenic process, which include the effect of the bacterial products of cholesterol and bile acid [55
Several studies have suggested that milk consumption may be related to a reduced risk of colorectal cancer [19
]. The main hypothesis underlying a possible protective effect of dairy products relates to their calcium content and to a lesser extent vitamin D, conjugated linoleic acid, sphingolipids, butyric acid, and fermentation products. As summarized in a review, cohort studies have quite consistently found a protective effect of total dairy products and milk intake, while findings of case-control studies were not very supportive [56
]. Milk is the predominant dairy product consumed in Shanghai. However, the level of milk intake in our study was much lower (70g/day) than in other cohort studies (range: 120-800g/day). We found suggestive evidence of an inverse association between milk intake and colorectal cancer.
It has been shown that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) can be activated in vivo by metabolic enzymes to exert their carcinogenic effect [57
]. Although an earlier epidemiological study showed that consumption of well-done/very well-done red meat and meat cooked using high temperature methods, such as roasting and possibly deep-frying, were related to an increased risk of colorectal cancer [58
], we found little evidence of a relationship between cooking methods and risk of cancer. In addition to low consumption of meat, it is noteworthy that roasting and deep-frying are not common cooking methods in our study population. Although we found an increased risk of colon cancer with ever use of ‘smoking’ as a cooking method, the frequency of using this method is low; only 9 % of women reported having used ‘smoking’ more than once per month, which prohibited a more detailed analysis.
Our study has several strengths. Dietary information was collected by in-person interview using a validated FFQ. The high participation rates for both baseline recruitment and cohort follow-ups have minimized selection bias. The two FFQs, assessed 2-3 years apart, improved the dietary assessment. The extensive information on lifestyle factors allowed for comprehensive evaluation and adjustment for potential confounders. The study, however, is limited by its relatively short follow-up time. It is possible that the dietary intake of participants who were diagnosed with colorectal cancer shortly after recruitment may have been affected by pre-clinical symptoms. However, excluding the first two years of observations and colorectal cancer patients from the analyses did not substantially alter the association between animal-origin food and cancer or colorectal cancer. Multiple comparisons and the relatively low amount of consumption of eel, shrimp and shellfish increase the possibility that our findings are due to chance. We could not examine the interactive effect of cooking methods and meat/fish intake for colon or rectal cancer separately due to a lack of statistical power. Continuing to follow this cohort for exposure updates, as is planned for the study, would yield more conclusive results.
In summary, in this large, population-based cohort study, we did not find an overall association between total consumption of animal origin food and risk of CRC. However, we did observe a positive association between CRC and consumption of eel, shrimp, shellfish, and eggs, as well as the “smoking” method of cooking. More research is needed to investigate the role of cholesterol and environmental pollution in the etiology of CRC.