The role of heterocyclic aromatic amines in colorectal cancer: the evidence from epidemiologic studies

Abstract

Since Dr. Sugimura’s discovery of heterocyclic aromatic amines (HAA) in broiled fish, many epidemiological studies have been conducted to investigate their role in human cancers, often focusing on colorectal cancer. The difficulty in measuring HAA exposure from meat and fish intake in these studies has resulted in inconsistent findings. Because studying individuals who may be particularly susceptible to the carcinogenic effects of HAA might facilitate the demonstration of a link with cancer, multiple studies have focused on individuals with the high activity phenotype for CYP1A2 and/or NAT2, the two main metabolic enzymes involved in the bioactivation of HAA. These investigations have also yielded inconsistent results. Two recent large pooled analyses of colorectal cancer studies have helped clarify the overall evidence. One was conducted in whites and reported no interaction of red meat intake and NAT2 genotype on risk in Whites. The other was conducted in Japanese and African Americans, two populations with high rates of the disease and a prevalence of the at-risk rapid NAT2 phenotype 10- and 2-fold greater than in whites, respectively. In those groups, a significant interaction was found, with the association of red meat with colorectal cancer being strongest among individuals with the rapid NAT2 phenotype, intermediate among those with the intermediate phenotype and not significant among those with the slow NAT2 phenotype. Recent research on biomarkers has focused on PhIP hair content, as a marker of exposure to HAA, and on DNA adducts using new sensitive quantitative methods, as markers of early biological effects. These advances, when brought to bear, may contribute greatly to the further elucidation of the carcinogenicity of HAA in humans.

Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer

“…The HCAs are transformed into genotoxic metabolites after being consumed and absorbed [ 158 , 159 ]. Numerous studies have postulated HCA as an oncogenic agent for CRC due to the correlation between greater HCA levels and a higher risk of CRC [ 160 , 161 , 162 ]. According to reports, HCAs can cause oxidative base damage, strand breakage, microsatellite instability, frameshift mutations, and microsatellite instability [ 163 ].…”

Inhibitory Effects of Some Hydrocolloids on the Formation of Advanced Glycation End Products and Heterocyclic Amines in Chemical Models and Grilled Beef Patties

“…This reaction usually occurs when creatinine, carbohydrates and amino acids are heated at high temperatures [11,12]. The IARC has classified some HAs as Class 2A and 2B human carcinogens [13] Polymers 2023, 15, 3914 2 of 13 as they can generate DNA adducts and increase the risk of cancers, especially liver, colon and prostate cancer [14].…”

Heterocyclic aromatic amines in spiced pork shoulder: content analysis and effects of soy sauce, cooking wine and sugar

“…The DNA adducts formed by the HAAs can induce mutations that may initiate/promote carcinogenesis (Ho et al ., 2015, 2017). A large number of studies showed that HAAs increased the risk of diseases, such as colorectal cancer, bladder cancer, prostate cancer, gastric cancer, and breast cancer (Koda et al ., 2017; Le Marchand, 2021; Lumbreras et al ., 2008; Pence et al ., 1998; Rabstein et al ., 2010). Therefore, the HAA content in the daily diet has attracted widespread attention.…”