Genetic polymorphisms in estrogen-metabolizing genes and breast cancer survival.

Long JR, Cai Q, Shu XO, Cai H, Gao YT, Zheng W
Pharmacogenet Genomics. 2007 17 (5): 331-8

PMID: 17429315 · DOI:10.1097/FPC.0b013e32801a3bfe

BACKGROUND - Estrogen plays a central role in the development and progression of breast cancer. The estrogen's effects are at least partially regulated by estrogen-metabolizing enzymes. The objective of the study is to investigate associations of breast cancer survival with genetic polymorphisms in several genes involved in estrogen metabolism (CYP1A1, CYP1A2, CYP1B1, COMT, and AhR).

METHODS - A cohort of 1140 patients aged between 25 and 64 years at the time of diagnosis for primary breast cancer during 1996-1998 were included in the study. Patients were followed for cancer recurrence and mortality through July 2005.

RESULTS - Associations were observed at rs4680 (Met158Val) in the COMT gene and rs4646903 (CYP1A1*2A) in the CYP1A1 gene. The adjusted hazard ratio for the rs4680 AA genotype (low enzyme activity genotype) was 1.6 (95% confidence interval, 1.1-2.4) compared with the GG genotype for disease-free survival. Adjusted hazard ratios for the rs4646903 CC genotype were 1.6 (95% confidence interval, 1.2-2.2) for disease-free survival and 1.4 (95% confidence interval, 1.0-2.1) for overall survival compared with the TT genotype. No apparent association was found for any of the other six single nucleotide polymorphisms evaluated in the AhR, CYP1A1, CYP1A2, and CYP1B1 genes.

CONCLUSION - Results from this study suggest that rs4680 in the COMT gene and rs4646903 in the CYP1A1 gene may be genetic markers for breast cancer prognosis in Chinese women.

MeSH Terms (16)

Adult Aryl Hydrocarbon Hydroxylases Breast Neoplasms Catechol O-Methyltransferase Cohort Studies Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A2 Cytochrome P-450 CYP1B1 Cytochrome P-450 Enzyme System Estrogens Female Genotype Humans Middle Aged Polymorphism, Single Nucleotide Receptors, Aryl Hydrocarbon

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