Meat Consumption, Heterocyclic Amines, NAT2, and the Risk of Breast Cancer

Mignone, L.; Giovannucci, Edward; Newcomb, Polly A.; Titus-Ernstoff, Linda; Trentham‐Dietz, Amy; Hampton, John M.; Orav, E. John; Willett, Walter C.; Egan, Kathleen M.

doi:10.1080/01635580802348658

Cited by 25 publications

(13 citation statements)

References 44 publications

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“…Our finding for red meat was consistent with the previous nested case-control studies in the NHS (14), Iowa Women’s Health Study (16), and population-based case-control studies with over 1000 cases (12, 13). In our study, 26% of the cases were also included in the previous study in the NHS (14).…”

Section: Discussionsupporting

confidence: 91%

“…The study used a comprehensive 192-item FFQ with a total of 63 foods and recipes in the FFQ to cover intake of individual meat items and mixed-dishes containing meat. For individual HCAs and MDM intake, few studies have examined the interaction with NAT 2 genotype, and no interactions between either HCAs (12, 15) or MDM (12) and NAT2 genotype were found on breast cancer risk, consistent with our findings.…”

Section: Discussionsupporting

confidence: 90%

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

Lee

Cox

et al. 2013

Nutrition and Cancer

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

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

Lee

Cox

et al. 2013

Nutrition and Cancer

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“…Previous studies have reported that PhIP DNA adduct levels in human breast tissue are higher in rapid than slow NAT2 acetylators (Zhu et al, 2003) and have suggested that rapid acetylator NAT2 phenotype increases colorectal (Lang et al, 1994; Chen et al, 1998; Le Marchand et al, 2001; Lilla et al, 2006; Ognjanovic et al, 2006; Cotterchio et al, 2008), breast (Deitz et al, 2000; Gallicchio et al, 2006), and lung (Chiou et al, 2005) cancer risk in individuals exposed to heterocyclic amine carcinogens. In contrast, other studies carried out with colorectal (Barrett et al, 2003; Barlak et al, 2006), breast (van der Hel et al, 2004; Ochs-Balcome et al, 2007; Mignone et al, 2009), and lung (Barlak et al, 2006) cancer do not support the association with rapid acetylator NAT2 phenotype. A much more robust effect of NAT2 phenotype has been noted for mutagenicity and DNA adduct formation from 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) (Bendaly et al, 2007).…”

Section: Discussionmentioning

confidence: 84%

Role of human CYP1A1 and NAT2 in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutagenicity and DNA adducts

Bendaly¹,

Metry²,

Doll³

et al. 2009

Xenobiotica

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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is carcinogenic in multiple organs and numerous species. Bioactivation of PhIP is initiated by PhIP N2- hydroxylation catalyzed by cytochrome P450s. Following N-hydroxylation, O-acetylation catalyzed by N-acetyltransferase 2 (NAT2) is considered a further possible activation pathway. Genetic polymorphisms in NAT2 may modify cancer risk following exposure. Nucleotide excision repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles were used to test the effect of CYP1A1 and NAT2 polymorphism on PhIP genotoxicity. Cells transfected with NAT2*4 had significantly higher levels of N-hydroxy-PhIP O-acetyltransferase (P = 0.0150) activity than cells transfected with NAT2*5B. Following PhIP treatment, CHO cell lines transfected with CYP1A1, CYP1A1/NAT2*4 and CYP1A1/NAT2*5B each showed concentration-dependent cytotoxicity and hypoxanthine phosphoribosyl transferase (hprt) mutagenesis not observed in untransfected CHO cells. dG-C8-PhIP was the primary DNA adduct formed and levels were dose-dependent in transfected CHO cells in the order: CYP1A1 < CYP1A1 & NAT2*5B < CYP1A1 & NAT2*4 although levels did not differ significantly (P>0.05) following one-way analysis of variance. These results strongly support activation of PhIP by CYP1A1 with little effect of human NAT2 genetic polymorphism on mutagenesis and DNA damage.

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“…b P trend calculated using the median of each quintile. Mignone et al, 2009). Interactions between meat (Zheng et al, 1999;Egeberg et al, 2008) or well-done meat (Zheng et al, 1999;Deitz et al, 2000) and xenobiotic-metabolising gene variants might explain these contradictory findings.…”

Section: Discussionmentioning

confidence: 96%

“…Iron may also be involved in breast cancer through interaction with catechol oestrogen metabolites or production of hydroxyl radicals (Liehr and Jones, 2001;Huang, 2003;. Limited epidemiological studies of meat mutagens (De Stefani et al, 1997;Delfino et al, 2000;Sinha et al, 2000;Steck et al, 2007;Sonestedt et al, 2008;Kabat et al, 2009;Mignone et al, 2009) and haem iron (Lee et al, 2004; are inconsistent.…”

mentioning

confidence: 99%

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

et al. 2009

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BACKGROUND: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. METHODS: Among 52 158 women (aged 55 -74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. RESULTS: Comparing the fifth to the first quintile, red meat (HR ¼ 1.23; 95% CI ¼ 1.00 -1.51, P trend ¼ 0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR ¼ 1.26; 95% CI ¼ 1.03 -1.55; P trend ¼ 0.12), and dietary iron (HR ¼ 1.25; 95% CI ¼ 1.02 -1.52; P trend ¼ 0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. CONCLUSION: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

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Meat Consumption, Heterocyclic Amines, NAT2, and the Risk of Breast Cancer

Cited by 25 publications

References 44 publications

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

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

Role of human CYP1A1 and NAT2 in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutagenicity and DNA adducts

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

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