After up to 7.2 years of follow-up, we ascertained 2,719 incident colorectal cancer cases (1,806 male and 913 female cases), of which 1,995 were colon cancers (1,150 proximal, 787 distal colon, 58 lacked definitive site information) and 724 were rectal cancers. We had stage information on 81% of the cases; of these, 43% were stage 1, 16% were stage II, 26% were stage III and 15% were stage IV at diagnosis. Individuals in the highest quintile of red meat intake were more likely to be non-Hispanic White, current smokers and to have a higher BMI compared with those in the lowest quintile; furthermore, they were less educated, less physically active, less likely to have a family history of colorectal cancer and consumed less calcium, fiber, fruits and vegetables (). The correlation between red meat intake and heme iron was high (rSpearman=0.82), as was the correlation between processed meat and both nitrate (rSpearman=0.93) and nitrite (rSpearman=0.97) in meat.
Selected means and proportions for characteristics of participantsin the NIH-AARP Diet and Health Study by red meat quintile from the RFQ (n=300,948)
Red meat and total processed meat (processed red and white meat) intake were both positively associated with colorectal cancer (HR for the fifth compared to the first quintile =1.24, 95% CI: 1.09-1.42, p-trend <0.001; HR=1.16, 95% CI: 1.01-1.32, p-trend= 0.017, respectively) (). Dividing red meat into processed red meat and non-processed red meat revealed similar risks (comparing the highest to the lowest quintiles: HR=1.11, 95% CI: 0.96-1.28, p-trend=0.083 for processed red meat; HR=1.13, 95% CI: 0.98-1.30, p-trend=0.002 for non-processed red meat). There was no evidence of an interaction by gender for either red (p-interaction=0.385) or processed meat (p-interaction=0.138). White meat was inversely associated with colorectal cancer (HR=0.85, 95% CI: 0.76-0.97, p-trend=0.017); this association was evident for chicken (HR=0.85, 95% CI:0.75-0.97, p-trend=0.020), but not for turkey (HR=1.02, 95% CI:0.90-1.17, p-trend=0.412), or fish intake (HR=0.95, 95% CI: 0.84-1.08, p-trend=0.903).
Meat intake and colorectal cancer in the NIH-AARP Diet and Health Study (n=300,948)
With further investigation by location, risks were elevated, though not all reached statistical significance, for both colon and rectal cancer for red meat (HR=1.21, 95% CI: 1.03-1.41, p-trend <0.001; HR=1.35, 95% CI: 1.03-1.76, p-trend=0.024, respectively) and processed meat (HR=1.11, 95% CI: 0.95-1.29, p-trend=0.057; HR=1.30, 95% CI: 1.00-1.68, p-trend=0.145, respectively) (); although the risks were slightly higher for rectal cancer, there was no evidence of sub-site heterogeneity for either red (p-heterogeneity=0.485) or processed meat (p-heterogeneity=0.320). Within the colon, the risks for proximal or distal tumors were not statistically significantly different for either red meat (HR=1.15, 95% CI: 0.94-1.41, p-trend=0.024; HR=1.29, 95% CI: 1.00-1.66, p-trend=0.018, respectively; p-heterogeneity=0.432) or processed meat (HR=1.09, 95% CI: 0.89-1.33, p-trend=0.245; HR=1.10, 95% CI: 0.86-1.41, p-trend=0.363, respectively; p-heterogeneity=0.497) (data not shown). In a lag analysis excluding the first two years of follow-up (n=1,941 colorectal cancer cases), the findings for both red and processed meat remained (HR=1.21, 95% CI: 1.03-1.42, p-trend=0.001; HR=1.19, 95% CI: 1.02-1.39, p-trend=0.013, respectively) (data not shown).
Using the detailed meat questionnaire, we examined specific components of meat in relation to colorectal cancer (). Interestingly, total iron intake and dietary iron were both inversely associated with colorectal cancer (HR=0.75, 95% CI: 0.66-0.86, p-trend <0.001; HR=0.75, 95% CI: 0.65-0.87, p-trend <0.001, respectively), although the more bioavailable heme iron was positively associated (HR=1.13, 95% CI: 0.99-1.29, p-trend=0.022). Although nitrate intake from processed meats was positively associated with this malignancy (HR=1.16, 95% CI: 1.02-1.32, p-trend=0.001), the association for nitrite did not quite reach statistical significance (HR=1.11, 95% CI: 0.97-1.25, p-trend=0.055). When we examined the highest compared to the lowest quintile of combined nitrate and nitrite intake (data not shown), there was an elevated risk for colorectal cancer (HR=1.14, 95% CI: 1.00-1.30, p-trend=0.019). Interestingly, an analysis of total dietary exposure revealed an inverse association in the highest quintile of dietary nitrate (HR=0.82, 95% CI: 0.71-0.95, p-trend=0.111) but null findings for total nitrite (HR=1.05, 95% CI: 0.92-1.21, p-trend=0.316) and colorectal cancer (data not shown). The findings for total dietary nitrate are likely due to the largest dietary sources of nitrate in our population, which includes several fruits and vegetables such as spinach, broccoli, potatoes and bananas.
Meat-related compounds and colorectal cancer in the NIH-AARP Diet and Health Study (n=300,948)
Individuals in the highest, compared with the lowest, quintile of MeIQx and DiMeIQx had an elevated risk of colorectal cancer (HR=1.19, 95% CI: 1.05-1.34, p-trend <0.001; HR=1.17, 95% CI: 1.05-1.29, p-trend <0.001, respectively) (). Neither PhIP nor B[a]P were associated with colorectal cancer; nevertheless, those in the highest quintile of mutagenic activity (a marker of all meat mutagens) had an elevated risk (HR=1.14, 95%CI: 1.01-1.29, p-trend=0.010). In sub-site analyses, the risk estimates for colon and rectal cancers were similar for most of the meat-related exposures, except for MeIQx, DiMeIQx and mutagenic activity, which were only associated with colon cancer (HR=1.26, 95% CI: 1.09-1.45, p-trend <0.001; HR=1.23, 95% CI: 1.10-1.39, p-trend <0.001; HR=1.19, 95% CI: 1.03-1.38, p-trend=0.002, respectively) ().