This is the first study to concurrently assess the association of meat intake, meat cooking methods and doneness levels, meat mutagens, heme iron and nitrite with prevalent colorectal adenomas in asymptomatic women undergoing colonoscopy. It is the first study to utilize a new NCI heme iron database to quantify heme iron intake based on laboratory measured meat samples. In our study, we found an increased risk of colorectal adenoma for women who consumed the highest amounts of red meat, pan fried meat, and the HCA MeIQx. Although there was no association for total iron, dietary iron, iron from supplements, or nitrite, there were positive associations between iron and heme iron from meat and colorectal adenoma although these associations did not reach statistical significance.
Our findings for red meat and pan fried meat agree with several previous studies that have observed positive associations between red meat and meat cooked at high temperatures and colorectal adenoma (5
). The motive for studying pan fried meat is based on the hypothesis that formation of HCAs during such high temperature cooking methods will increase the risk of neoplasia; therefore, it is particularly interesting that we also observed a positive association with MeIQx, which has been associated with increased risk of colorectal adenoma in previous studies (14
). Unlike some previous studies, we did not observe an elevated risk for grilled meat (17
) or for well/very well done meat (14
Although some studies have linked high intake of processed meat intake to an increased risk of colorectal adenoma (40
), we did not observe such an association in our study population, which had a relatively low intake of processed meat and thus low levels of nitrite from meat. The one previous study that utilized the NCI nitrite database found a two-fold increased risk of colorectal adenoma for those in the highest quartile of nitrate and nitrite intake compared to the lowest quartile; however, the range of intake of processed meat was higher in the previous study compared to ours (40
). Consequently, our study may have lacked statistical power to assess the association of nitrite with colorectal adenoma.
Our null findings for dietary iron are similar to those reported by three previous studies of colorectal adenoma (27
). Several cohort studies have examined the association between dietary iron (34
) or iron stores (34
) and colorectal cancer, but results have been inconclusive. Nelson et al., evaluated 33 case-control studies and concluded that higher dietary iron and iron stores were associated with an increased risk of colorectal cancer (56
). However, results from a recent nested case-control study among male smokers found inverse associations between several serum iron indices and colon cancer, but not rectal cancer (57
). The inconsistency in the literature might be due to the different study populations, as well as the different sources and types of iron evaluated in these studies. Future research may also need to consider role of individual variation in genes related to iron absorption and metabolism in colorectal neoplasia. Finally, the role of iron in colorectal carcinogenesis is most likely very complex, as excess exposure to iron could be at the systemic level through excess iron absorption or directly through the lumen due to the passage of excess dietary iron through the gastrointestinal tract.
Our findings do not show a clear association between iron and heme iron from meat and colorectal adenoma in women, although there was a suggestion of an increased risk. This is the first study to assess heme iron intake using a database based on laboratory measured values of heme iron in various meats cooked by different methods and to varying degrees of doneness. Previous studies of colorectal cancer that have attempted to evaluate heme iron intake using a proportion of total iron (32
) or by employing a methodology that accounts for varying levels of heme iron by meat type (31
), have yielded inconsistent results. In this study, heme iron intake estimated as 40% of iron from those meats in the heme iron database was highly correlated with the heme iron database values and most individuals were classified in the same quartile of intake. However, had we only assessed heme iron as 40% of iron from all meats, as done in previous research, the risk estimate would have been completely null.
Our current findings on heme iron may be somewhat limited as this population of women had a higher consumption of white meat as compared to red meat and a narrow range of cooking methods and doneness levels. In addition, heme iron intake is most likely underestimated in this population as the heme database only accounted for 57.3% of the red meat intake in our population and we may have lacked the power to observe a statistically significant association for a low range of intake. In light of the inconsistent findings for heme iron, additional studies are necessary. The NCI heme iron database should also be investigated in other larger populations to further evaluate current estimation methods of exposure to heme iron.
The strengths of our study include colonoscopy confirmed colorectal adenoma status for all participants, detailed exposure assessment of meat intake, cooking methods and doneness levels, analysis of multiple potential mechanisms, and a high participation rate. This dataset provided a unique opportunity to comprehensively examine a wide range of meat-related exposures among asymptomatic women with little risk of dietary changes due to disease status. Participants also completed questionnaires prior to colonoscopy eliminating recall bias. Limitations of this study include the cross-sectional rather than longitudinal design, as well as the evaluation of usual dietary intake only during the year prior to colonoscopy, which may not be the time period most relevant to the development of colorectal adenoma. Although this study utilized comprehensive methods of assessment for meat, meat cooking methods, and doneness levels, the possibility of some degree of measurement error remains. As in any observational study, it is possible that the observed association is due to unmeasured or residual confounding, although this study did assess all known potential confounders. We also were not able to evaluate genetic variation that may be involved in colorectal carcinogenesis. Finally, the generalizability of these results is limited to predominantly Caucasian and highly educated women.
This is the first study to assess meat intake and the currently hypothesized potentially carcinogenic components of meat in relation to colorectal adenoma in a population of asymptomatic women undergoing screening colonoscopy. In this population, there was an increased risk of colorectal adenoma with high intake of red meat, pan fried meat, and, the HCA MeIQx. Future research on meat and colorectal neoplasia should focus on assessing all meat-related exposures to enhance our understanding of the mechanisms for the role of meat in cancer. Given our small sample size, evaluation of heme iron and nitrite from meat in large, prospective cohort studies is needed to clarify the role of these exposures in carcinogenesis.