Comparative analysis of SNP in estrogen-metabolizing enzymes for ovarian, endometrial, and breast cancers in Novosibirsk, Russia.
We estimated the frequency of CYP1A1, CYP1A2, CYP1B1, CYP19, and SULT1A1 allelic variants in a female population of the Novosibirsk district and their association with the elevated risk of breast (BC), ovarian (OC), and endometrial (EC) cancers. Significant differences (OR = 2.34, p = 0.0002) in the allele distributions for CYP1A1 M1 polymorphism between patients with BC (n = 118) and controls (n = 180) were found. No significant difference in both genotype and allele distributions for CYP1A1 polymorphisms in patients with OC (n = 96) and EC (n = 154) was observed. Remarkable differences in the allele and genotype distributions for CYP1A2*1F polymorphism in patients with BC or OC were found (OR = 0.26, p = 0.0000005 and OR = 0.34, p = 0.00000002). There were no differences for this polymorphism in women with EC. In patients with BC no significant differences were found in genotype and allele distributions for R264C polymorphism in the CYP19 gene. The frequency of a mutant CYP19 heterozygote genotype C/T was higher in patients with OC and EC compared with healthy women (OR = 3.87, p = 0.001 and OR = 3.73, p = 0.0004, respectively). Comparison of allele frequencies revealed a deficiency of an allele A of SULT1A1*2 in patients with OC (OR = 0.64, p = 0.019) compared with controls. No differences were found in the genotype and allele distributions for SULT1A1 polymorphism between patients with BC and EC and controls. In addition, there were no difference in allele and genotype distributions for CYP1B1 119G-->T polymorphism between BC and control. In conclusion, these results support the hypothesis that susceptibility gene alleles of estrogen-metabolizing enzymes may differentially influence risk for woman hormone-dependent cancers.
Gulyaeva
Lyudmila F
LF
Institute of Molecular Biology and Biophysics, Academy of Medical Sciences, Novosibirsk, Russia.
Mikhailova
Olga N
ON
PustyInyak
Vladimir O
VO
Kim
Inessa V
IV
Gerasimov
Alexei V
AV
Krasilnikov
Sergey E
SE
Filipenko
Maxim L
ML
Pechkovsky
Eugene V
EV
D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases; D015239:Arylsulfotransferase / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012426:Russia
D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human