N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer.
The role of N-acetyltransferase 2 (NAT2) polymorphism in breast cancer is still unclear. We explored the associations between potential sources of exposure to aromatic and heterocyclic amines (AHA), acetylation status and receptor-defined breast cancer in 1020 incident cases and 1047 population controls of the German GENICA study. Acetylation status was assessed as slow or fast. Therefore, NAT2 haplotypes were estimated using genotype information from six NAT2 polymorphisms. Most probable haplotypes served as alleles for the deduction of NAT2 acetylation status. The risks of developing estrogen receptor alpha (ER) and progesterone receptor (PR)-positive or negative tumors were estimated for tobacco smoking, consumption of red meat, grilled food, coffee, and tea, as well as expert-rated occupational exposure to AHA with logistic regression conditional on age and adjusted for potential confounders. Joint effects of these factors and NAT2 acetylation status were investigated. Frequent consumption of grilled food and coffee showed higher risks in slow acetylators for receptor-negative tumors [grilled food: ER-: odds ratio (OR) 2.57, 95% confidence interval (CI) 1.07-6.14 for regular vs. rare; coffee: ER-: OR 2.55, 95% CI 1.22-5.33 for >or=4 vs. 0 cups/day]. We observed slightly higher risks for never smokers that are fast acetylators for receptor-positive tumors compared with slow acetylators (ER-: OR 1.32, 95% CI 1.00-1.73). Our results support differing risk patterns for receptor-defined breast cancer. However, the modifying role of NAT2 for receptor-defined breast cancer is difficult to interpret in the light of complex mixtures of exposure to AHA.
Rabstein
Sylvia
S
BGFA-Research Institute of Occupational Medicine of the German Social Accident Insurance, Ruhr University Bochum, Germany. rabstein@bgfa.de
Brüning
Thomas
T
Harth
Volker
V
Fischer
Hans-Peter
HP
Haas
Susanne
S
Weiss
Tobias
T
Spickenheuer
Anne
A
Pierl
Christiane
C
Justenhoven
Christina
C
Illig
Thomas
T
Vollmert
Caren
C
Baisch
Christian
C
Ko
Yon-Dschun
YD
Hamann
Ute
U
Brauch
Hiltrud
H
Pesch
Beate
B
D000107:Acetylation; D000368:Aged; D000588:Amines / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004781:Environmental Exposure; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
D000588:Amines; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone; D014028:Tobacco Smoke Pollution; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human