The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer

Cytochrome P450 1B1 (CYP1B1) is a major enzyme in the initial catabolic step of estradiol (E2) metabolism and belongs to the multitude of genes regulated by the estrogen receptor alpha (ERα). The common non-synonymous polymorphisms CYP1B1_1358_A>G and CYP1B1_1294_C>G increase CYP1B1 enzymatic activity. Given a relationship between CYP1B1 and breast tumor E2 level as well as E2 level and breast tumor ERα expression it is of interest to know whether CYP1B1 polymorphisms have an impact on the ERα status of breast cancer. We genotyped the GENICA population-based breast cancer case–control collection (1,021 cases, 1,015 controls) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and investigated in cases the association between genotypes and tumor ERα status (739 ERα positive cases; 212 ERα negative cases) by logistic regression. We observed a significant association between the homozygous variant CYP1B1_1358_GG genotype and negative ERα status (P = 0.005; OR 2.82, 95% CI: 1.37–5.82) with a highly significant Ptrend for CYP1B1_1358_A>G and negative ERα status (P = 0.003). We also observed an association of CYP1B1_1358_GG and negative PR status (P = 0.015; OR 2.36, 95% CI: 1.18–4.70) and a Ptrend of 0.111 for CYP1B1_1358_A>G and negative progesterone receptor (PR) status. We conclude that the CYP1B1_1358_A>G polymorphism has an impact on ERα status in breast cancer in that the CYP1B1_1358_GG genotype known to encode higher CYP1B1 activity is associated with ERα negativity.