Genetic polymorphisms of the CYP19A1 gene and breast cancer survival.
The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus may be related to the progression of breast cancer. We examined the association between CYP19A1 genetic polymorphisms and breast cancer survival in a cohort of 1,136 patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and who has donated a DNA sample to the study. Patients were followed for cancer recurrence and mortality through July 2005. Nineteen haplotype tagging single-nucleotide polymorphisms (SNP) in the CYP19A1 gene were evaluated. For each of the five SNPs located in haplotype block 2, patients homozygous for the minor alleles had a reduced 5-year disease-free survival rate compared with those carrying the major allele. The age-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were 1.5 (1.1-2.1), 2.1 (1.2-3.6), 1.5 (1.1-2.0), 1.4 (1.0-2.0), and 1.4 (1.0-2.0) for hCV1664178, rs12900137, rs730154, rs936306, and rs1902586, respectively. Haplotype analyses showed that the haplotype CCCTA (all minor alleles of the five SNPs in block 2) was associated with decreased disease-free survival (HR, 1.9; 95% CI, 1.1-3.3). The nonsynonymous SNP, rs700519 (Arg264Cys), located in haplotype block 4, was also associated with breast cancer survival. The age-adjusted HR for the Cys/Cys (T/T) genotype was 2.2 (95% CI, 1.2-4.1) for overall survival and 2.1 (95% CI, 1.1-3.9) for disease-free survival, compared with those carrying the Arg (C) allele. These results suggest that polymorphisms in the CYP19A1 gene may have effects on breast cancer prognosis.
Long
Ji-Rong
JR
Department of Medicine, Center for Epidemiologic Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2587, USA.
Kataoka
Nobuhiko
N
Shu
Xiao-Ou
XO
Wen
Wanqing
W
Gao
Yu-Tang
YT
Cai
Qiuyin
Q
Zheng
Wei
W
D000328:Adult; D001141:Aromatase / Q000235:genetics* / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D016896:Treatment Outcome
D001141:Aromatase