Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype

Citation
Rj. Delfino et al., Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype, CARCINOGENE, 21(4), 2000, pp. 607-615
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
21
Issue
4
Year of publication
2000
Pages
607 - 615
Database
ISI
SICI code
0143-3334(200004)21:4<607:BCHAAF>2.0.ZU;2-M
Abstract
Breast cancer risk has been hypothesized to increase with exposure to heter ocyclic aromatic amines (HAAs) formed from cooking meat at high temperature . HAAs require enzymatic activation to bind to DNA and initiate carcinogene sis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic p olymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-l-methyl-6-phenylimidazole[4,5-b]pyrid ine (PhIP), 2-amino-3,8-dimethylimidazo[4,5 -f]quinoxaline (MeIQx)) and 2-a mino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx)] intake. Women wer e recruited with suspicious breast masses and questionnaire data were colle cted prior to biopsy to blind subjects and interviewers to diagnoses. For 1 14 cases with breast cancer and 280 controls with benign breast disease, NA T2 genotype was determined using allele-specific PCR amplification to detec t slow acetylator mutations, HAAs were estimated from interview data on mea t type, cooking method and doneness, combined with a quantitative HAA datab ase, Logistic regression models controlled for known risk factors, first in cluding all controls, then 108 with no or low risk (normal breast or no hyp erplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia , complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer , These Californian women ate more white than red meat (control median 46 v ersus 8 g/day), There were no significant associations of breast cancer wit h red meat for any doneness, White meat was significantly protective (>67 v ersus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chi cken, including well done, pan fried and barbecued chicken, MeIQx and DiMeI Qx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken. Results were unchanged using low or high risk controls or dropping 30 in situ cases. There was no interaction between NAT2 and HAAs. These findings do not support a role for HAAs from meat or NAT2 in the etiology of breast cancer. Further research is needed to explain the white meat association.