Association between polymorphisms in estrogen metabolism genes and breast cancer development in Chinese women: A prospective case–control study

We comprehensively identified polymorphisms in estrogen-metabolizing genes that may be associated with breast cancer initiation in Chinese women, via an ongoing prospective case–control study. An ongoing prospective case–control study of 427 female case patients diagnosed with breast cancer from August 2013 to March 2015 and 536 women (case controls) with no prior history of cancer or benign breast tumors was performed. Buccal cell specimens were obtained using the cotton swabbing method. DNA was extracted from the buccal cells using the phenol/chloroform method. Genotype was carried out for 5 single nucleotide polymorphisms (rs4646903, rs1056836, rs1695, rs4970737, and rs4680) using direct sequencing. The polymorphic genotypes of glutathione S-transferase (GSTP1) (P = .044) and catechol-O-methyltransferase (COMT) (P = .008) showed significantly different distributions, while that of cytochrome P450 (CYP1B1) (P = .051) showed a slight difference in distribution between healthy women and patients with breast cancer. Individuals with homozygous variant genotypes for GSTP1 or COMT exhibited a higher risk of developing breast cancer than those with wild-type genotypes; however, for CYP1B1, the homozygous variant genotype was associated with a lower risk, and the heterozygous genotype for these 3 genes was not associated with breast cancer development. An individual's risk of breast cancer is only influenced by the specific combination of risk-associated alleles of COMT and GSTP1, despite the protective effects of the homozygous CYP1B1 genotype revealed by univariate analysis.