Studies on CYP1A1, CYP1B1 and CYP3A4 gene polymorphisms in breast cancer patients.
BACKGROUND
The role of CYP1A1, CYP1B1 and CYP3A4 polymorphism in pathogenesis of breast cancer has not been fully elucidated. From three CYP1A1 polymorphisms *2A (3801T>C), *2C (2455A>G), and *2B variant, which harbors both polymorphisms, the *2A variant is potentially carcinogenic in African Americans and the Taiwanese, but not in Caucasians, and the CYP1B1*2 (355G>T) and CYP1B1*3 (4326C>G) variants might increase breast cancer risk. Although no association of any CYP3A4 polymorphisms and breast cancer has been documented, the CYP3A4*1B (392A>G) variant, correlates with earlier menarche and endometrial cancer secondary to tamoxifen therapy.


OBJECTIVE
The present study was designed to investigate the frequency of CYP1A1, CYP1B1 and CYP3A4 polymorphisms in a sample of breast cancer patients from the Polish population and to correlate the results with the clinical and laboratory findings.


METHODS
The frequencies of CYP1A1*2A; CYP1A1*2C; CYP1B1*3; CYP3A4*1B CYP3A4*2 polymorphisms were determined in 71 patients aged 36-87, with primary breast cancer and 100 healthy individuals. Genomic DNA was extracted from the tumor and individual gene fragments were PCR-amplified. The polymorphisms were determined by RFLP and were correlated with the patients' TNM stage, grade, estrogen and progesterone receptor status as well as the level of c-erbB-2 protein.


RESULTS
CYP1A1 polymorphisms were more frequent in younger patients and in the patients with high level of c-erbB-2 protein. No correlation between these polymorphisms and the cancer stage or grade, as well as the receptor status was demonstrated.


CONCLUSIONS
CYP1A1 polymorphisms probably predispose to an earlier onset of breast cancer and might be associated with higher c-erbB-2 protein level, but further studies on a much larger group are required to substantiate our findings.
Ociepa-Zawal
Marta
M
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland.
Rubiś
Błazej
B
Filas
Violetta
V
Breborowicz
Jan
J
Trzeciak
Wiesław H
WH
D000328:Adult; D000367:Age Factors; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D044465:White People / Q000235:genetics
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human