Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 111, Issue 1, Pages 171-177Publisher
SPRINGER
DOI: 10.1007/s10549-007-9762-x
Keywords
CYP1B1; polymorphism; breast cancer; ER alpha status
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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 (ER alpha). 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 ER alpha expression it is of interest to know whether CYP1B1 polymorphisms have an impact on the ER alpha 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 ER alpha status (739 ER alpha positive cases; 212 ER alpha negative cases) by logistic regression. We observed a significant association between the homozygous variant CYP1B1_1358_GG genotype and negative ER alpha status (P = 0.005; OR 2.82, 95% CI: 1.37-5.82) with a highly significant P (trend) for CYP1B1_1358_A > G and negative ER alpha 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 P(trend) 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 ER alpha status in breast cancer in that the CYP1B1_1358_GG genotype known to encode higher CYP1B1 activity is associated with ER alpha negativity.
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