[Relationship between estrogen-biosynthesis gene (CYP17, CYP19, HSD17beta1) polymorphisms and breast cancer].
OBJECTIVE
To explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17beta1) and risk of breast cancer.


METHODS
A matched case-control study was designed. From May 2007 to July 2008, 200 pairs of subjects with and without breast cancer were enrolled, who were matched by age and menstruation status. Demographical characteristics, dietary factors and reproductive factors were investigated by questionnaire. CYP17 locus 1931 (T-->C), CYP19 codon 264 (Arg-->Cys) and HSD17beta1 locus 1954 (A-->G) were identified by AS-PCR (allele-specific PCR). The gene-gene interaction were analyzed with the MDR model (multifactor dimensionality reduction). Based on the results of MDR model, an unconditional logistic regression model was simulated to estimate the ORs of interaction factors and other risk factors.


RESULTS
The main effect of CYP17, CYP19 and HSD17beta1 susceptible genotypes were not correlated to breast cancer (OR approximately 1, P > 0.05). The positive interaction effect between CYP17 (T 1931C) and HSD17beta1 (A1954G) was discovered by MDR model with a statistically significant difference (Sign test, P = 0.05). The model's testing balance accuracy was 56.00%, and crossing validation consistency was 10/10. Multivariable unconditional logistic regression showed that after adjusting BMI, intake of estrogen, age of first birth, number of abortion and period of breast feeding, the interaction item of CYP17 (T1931C) and HSD17beta1 (A1954G) was strongly and positively correlated to breast cancer (OR = 2.52, 95%CI = 1.54 to 4.11).


CONCLUSIONS
The estrogen-biosynthesis genes CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphism may jointly increase the risk of breast cancer.
Wang
Yuan-ping
YP
West-China School of Public Health, Sichuan University, Chengdu 610041, China.
Li
Hui
H
Li
Jia-yuan
JY
Yuan
Ping
P
Yang
Fei
F
Lei
Fang-ming
FM
Pang
Yi
Y
Guo
Jie
J
D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase