Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.
OBJECTIVE
Circulating estrogen levels have been related to the risk of several female cancers. Blood levels of estrogen are controlled by estrogen synthesis enzymes. Genetic variation of estrogen genes thus may influence circulating estrogen levels. We investigated the associations of genetic polymorphisms in CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of sex hormones among postmenopausal Chinese women.


METHODS
Included in this study were 345 postmenopausal community controls from a population-based case-control study conducted in Shanghai. Fasting blood samples from those women were measured for blood estradiol, estrone, estrone sulfate, and testosterone. A total of 19 genetic polymorphisms in CYP19A1 were genotyped using ABI7900 or PCR-restriction fragment length polymorphism methods. Differences in plasma levels of hormones by genotype were examined using variance analysis.


RESULTS
The geometric means of plasma levels of estradiol, estrone, estrone sulfate, and testosterone were 10.1, 16.8, 969.0, and 202.9 pg/ml, respectively, for this study population. We found that plasma levels of estrone were associated with rs28566535 (P=0.0180), rs730154 (P=0.0141), and rs936306 (P=0.0274) in block 2. In the same block, the haplotype CGCTA was related to level of estrone (P=0.0064). Single nucleotide polymorphism rs1902584 in block 1 was associated with estradiol only in overweight postmenopausal women. No clear association with sex hormones was noted for the other genetic polymorphisms evaluated in the study.


CONCLUSIONS
Single nucleotide polymorphisms in blocks 1 and 2 of the CYP19A1 gene are related to plasma levels of estrogen among postmenopausal Chinese women and may therefore play an important role in the etiology of hormone-related cancers.
Cai
Hui
H
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN 37203-1738, USA. hui.cai@vanderbilt.edu
Shu
Xiao Ou
XO
Egan
Kathleen M
KM
Cai
Qiuyin
Q
Long
Ji-Rong
JR
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D001141:Aromatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002681:China; D016001:Confidence Intervals; D004958:Estradiol / Q000097:blood; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*
D005819:Genetic Markers; D012739:Gonadal Steroid Hormones; D004958:Estradiol; D001141:Aromatase