CYP17 (T-34C) and CYP19 (Trp39Arg) polymorphisms and their cooperative effects on breast cancer susceptibility.
BACKGROUND
Breast cancer is the commonest cancer among women in industrialized countries. Most sporadic breast carcinomas are likely to be caused by low-penetrance genes. Genes encoding enzymes involved in estrogen and carcinogen metabolism are among these low-penetrance genes. In this study, for the first time the T/C (A1/A2) polymorphism at the 5' untranslated region (UTR) of CYP17 and the Arg/Trp (T/C) polymorphism at codon 39 of CYP19 among genes regulating endogenous estrogen levels was studied.


METHODS
Fifty-five female breast cancer patients and ninety-one controls took part in the study. DNA was extracted from paraffin-embedded tissues for the patients and from blood cells for the controls. The distribution of genotypes was determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques.


RESULTS
The frequency of the TC genotype of CYP19 was significantly higher in the patient group (p<0.001, kappa(2): 12.31, OR: 7.30, 95% CI: 2.29-25.64). CYP17 frequencies were similar to those in Caucasian populations. In combined analysis, when the high risk alleles were evaluated together, the results reached significance (p=0.006, kappa(2)=7.01, OR: 2.53, %95 CI: 1.26-5.07) for the A2 allele of CYP17 and the C allele of CYP19, being more frequent in the patient group compared to the control. The risk possesed by the TC varient of CYP19 was reduced when evaluated with A1, the protective allele of CYP17 (p=0.082). The cumulative protective effects of both A1 allele and the TT genotype were ascertained to occur significantly less frequently in the patient group (p=0.001, kappa(2): 10.53, OR: 8.47, %95 CI: 1.9-37.04).


CONCLUSIONS
The results were consistent with the individual studies of CYP17 and CYP19 in the literature, however, in combined analysis of the alleles of the two genes, the frequency of high risk alleles was higher and the frequencies of low risk alleles were lower in the patient group. The CYP17 A1 + CYP19 TT haplotype may be protective for breast cancer.
Institute of Experimental Medical Research, Department of Molecular Medicine, University of Istanbul, Turkey.
Bora M
BM
Tüzüner
Tülin
T
Oztürk
Halil I
HI
Kisakesen
Sennur
S
Ilvan
Calay
C
Zerrin
Oğuz
O
Oztürk
Turgay
T
Isbir
D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
D004273:DNA, Neoplasm; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase