Polymorphisms in Xenobiotic Metabolizing Genes, Intakes of Heterocyclic Amines and Red Meat, and Postmenopausal Breast Cancer

Abstract

Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are cooked at high temperature and for long duration. The findings from previous studies on the relation between HCAs and breast cancer are inconsistent, possibly due to genetic variations in the enzymes metabolizing HCAs. To evaluate whether the associations of intakes of estimated HCAs, meat-derived mutagenicity (MDM), and red meat with risk of postmenopausal breast cancer were modified by N-acetyltransferase 2 (NAT2) acetylator genotype or cytochrome P450 1A2 -164 A/C (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases and 981 controls within a prospective cohort, the Nurses’ Health Study (NHS). HCAs and MDM intakes were derived using a cooking method questionnaire administered in 1996. NAT2 acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM, and red meat were not associated with risk of postmenopausal breast cancer. There was also no interaction between NAT2 acetylator genotype or CYP1A2 polymorphism and HCAs and MDM and red meat intake in relation to breast cancer. These results do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes involved in the metabolism of HCAs may modify the associations between intakes of red meat or meat-related mutagens and breast cancer risk.

Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk

“…Similar findings have been reported for the Nashville Breast Health Study [81] and the NIH-AARP Diet and Health Study among both, pre- and postmenopausal women [82]. Red and processed meats consist of heterocyclic amines, n -nitroso compounds, and polycyclic aromatic hydrocarbons, all of which are potential human carcinogens [17, 83]. Meat also contains animal fats and saturated fats, which are associated with the increased risk of breast cancer, in particular of the ER+/ER− and HER2-subtypes [84–86].…”

Consumption of red and processed meat and breast cancer incidence: A systematic review and meta‐analysis of prospective studies

“…In addition, three nested case–control studies and two clinical trial studies (not testing either red meat or processed meat) met inclusion criteria for red/processed meat. Furthermore, two studies met inclusion criteria regarding the interaction between red meat consumption and NAT2 polymorphisms on risk of breast cancer (Table ).…”

“…Therefore, these differences in enzyme activity may modify the carcinogenic effect of red meat. However, regarding the interaction between meat consumption and NAT2 polymorphisms on risk of breast cancer, evidence in epidemiological studies is sparse and conflicting, and it has not been evaluated in published meta‐analyses.…”

Food Processing and the Mediterranean Diet

“…The evidence for a causal relationship between processed meat and breast cancer is limited and mainly observed in case-control studies where a genetic polymorphism in N-acetyltransferase 2 has been investigated in relation to the presence of HCA in foods (e.g., [ 209 ]). However, recent evidence does not suggest that polymorphisms in genes that metabolize HCAs ( N -acetyltransferase 2 and CYP 1A12) modify colon or breast cancer risk [ 210 , 211 ]. In the National Institutes of Health (NIH)—AARP Diet and Health prospective study, there is suggestive evidence implicating HCAs found in red meat cooked at high temperatures in gastric cardia and non-cardia adenocarcinomas although the association never reached statistical significance [ 212 ].…”