Red meat-derived heterocyclic amines increase risk of colon cancer: a population-based case-control study

Abstract

Formation of mutagenic heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) is one pathway believed to drive the association of colon cancer with meat consumption. Limited data exist on the associations of individual HCAs and PAHs in red or white meat with colon cancer. Analyzing data from a validated meat preparation questionnaire completed by 1062 incident colon cancer cases and 1645 population controls from an ongoing case-control study, risks of colon cancer were estimated using unconditional logistic regression models, comparing the fourth to the first quartile of mutagen estimates derived from a CHARRED based food frequency questionnaire. Total dietary intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) [adjusted odds ratio (aOR) = 1.87, 95% confidence interval (CI) = 1.44-2.44, P(trend) < 0.0001], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) (aOR = 1.68, 95% CI = 1.29-2.17, P(trend) = 0.001) and meat-derived mutagenic activity (aOR = 1.77, 95% CI = 1.36-2.30, P(trend) < 0.0001) were statistically significantly associated with colon cancer risk. Meat type specific analyses revealed statistically significant associations for red meat-derived MeIQx, DiMeIQx, and mutagenic activity but not for the same mutagens derived from white meat. Our study adds evidence supporting red meat-derived, but not white-meat derived HCAs and PAHs, as an important pathway for environmental colon cancer carcinogenesis.

FIGURE 1. Meat doneness preferences, ORs and 95% CIs for doneness category by meat type

ORs (95% CI) adjusted by unconditional logistic regression for age, sex, race, WHR, average daily total caloric intake, family history of colorectal cancer and ever regular NSAID use. ● Lightly brown/rare (referent); ■ Medium brown/pink; ▲ Heavily browned or heavily browned/ blackened. Because of missing data on mutagen intake the following were excluded from all analyses in this figure: for total mutagen estimates 56 cases and 41 controls; for red meat-derived mutagen estimates 65 cases and 71 controls; for white meat-derived mutagen estimates 73 cases and 71 controls. ¹ “Chicken outside doneness” was included as an adjusting variable. ² “Red meat outside doneness” was included as an adjusting variable. ³ “Red meat inside doneness” was included as an adjusting variable.

FIGURE 2. Mutagen-related compounds, ORs and 95% CIs for meat-derived mutagenic activity by meat subtype

ORs (95% CI) adjusted by unconditional logistic regression for age, sex, race, WHR, average daily total caloric intake, family history of colorectal cancer and ever regular NSAID use. For each individual mutagen derived from a meat type (red or white meat), the opposite meat type for the individual mutagen was included as an adjusting variable (e.g., for red meat-derived activity, white meat-derived activity was included as adjusting variable). ● Quartile 1 (referent); ■ Quartile 2; ▲ Quartile 3; ◆ Quartile 4. Because of missing data on mutagen intake the following were excluded from all analyses in this figure: for total mutagen estimates 56 cases and 41 controls; for red meat-derived mutagen estimates 65 cases and 71 controls; for white meat-derived mutagen estimates 73 cases and 71 controls.