CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population.
We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1-9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07-6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30-19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03-2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11-5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.
Sillanpää
Pia
P
Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, Helsinki, Finland.
Heikinheimo
Liisa
L
Kataja
Vesa
V
Eskelinen
Matti
M
Kosma
Veli-Matti
VM
Uusitupa
Matti
M
Vainio
Harri
H
Metsola
Katja
K
Hirvonen
Ari
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D005387:Finland; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D016896:Treatment Outcome; D044465:White People
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1