Abstract
Heterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated.
Highlights
Heterocyclic aromatic amines (HAAs), which are formed by the reaction of creatine or creatinine, amino acids and sugars in meat and fish to cooking at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models [1–3]
Development of dietary assessment method We developed a practical method for assessing dietary HAA intake using a food frequency questionnaire (FFQ) used for the Japan Public Health Center-based Prospective Study (JPHC study) [16]
PhIP levels were significantly increased with a higher category of energy-adjusted PhIP intake for three groups (Fig. 1). These findings suggest that our FFQ for middle-aged or older Japanese is reasonably valid for the assessment of HAA intake, which in turn allows its use in future epidemiological studies of the association between HAA intake and cancer risk by ranking individuals by dietary intake of HAAs
Summary
Heterocyclic aromatic amines (HAAs), which are formed by the reaction of creatine or creatinine, amino acids and sugars in meat and fish to cooking at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models [1–3]. Dietary intake of the following seven HAAs was calculated: PhIP, MeIQx, MeIQ, 4,8-DiMeIQx, 2-amino3,7,8-trimethylimidazo [4,5-f] quinoxaline (7,8DiMeIQx), 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indole (Trp-P-1). We failed to detect significant associations between dietary HAA intake and the risk of colorectal cancer based on a hospital-based case-control
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