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

Abstract

Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations. HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database. Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) 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 versus 8 g/day). There were no significant associations of breast cancer with red meat for any doneness. White meat was significantly protective (>67 versus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chicken, including well done, pan fried and barbecued chicken. MeIQx and DiMeIQx 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.

Cooking of meat and fish in Europe—results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

“…Not only the quantity of red meat intake is of interest but also the cooking of it. Associations between the consumption of fried, grilled, barbecued or pan-fried red meat and the risk of colon cancer (Schiffman & Felton, 1990), colorectal adenomas , breast cancer (Zheng et al, 1999) and stomach cancer (Ward et al, 1997) were found, but there are several investigations that were not able to detect any association (Delfino et al, 2000;Gertig et al, 1999;Ambrosone et al, 1998). In the present study, the preparation of red meat shows a great variability across the participating countries and regions.…”

Meat consumption and risk of breast cancer in the UK Women's Cohort Study

“…Previous studies have tended to find inverse relationships with consumption of poultry (Delfino et al, 2000;Ronco et al, 2003) and have generally been statistically non-significant. Our findings do not provide strong evidence of an association with poultry intake and breast cancer in either pre-or postmenopausal women.…”

GSTM1 Null Genotype, Red Meat Consumption and Breast Cancer Risk (The Netherlands)

“…Due to differences in enzyme activity, polymorphisms in genes of metabolizing enzymes may increase breast cancer risk in women who are exposed to carcinogens from meat intake. Results on meat consumption, metabolic polymorphisms and their role in breast cancer are conflicting [13][14][15][16][17][18][19].…”