Associations between genetic variants in hormone-related genes and breast cancer risk in pre- and post-menopausal women.

aModels were adjusted for ethnicity (Caucasian, African American, Hispanic) and through matching, were also adjusted for age at blood donation, duration of sample storage, and menopausal status.bModels were adjusted for ethnicity (Caucasian, African American, Hispanic), age at first birth/parity (≤20 years, 21–25 years, 26–30 years, >30 years, nulliparous), age at menarche, family history of breast cancer, ever use of HRT, and BMI, and through matching, were also adjusted for age at blood donation, duration of sample storage, and menopausal status.cFor each genetic variant (except PGR-12 rs1042838), the genotype associated with higher estrogen exposure (see below) was assigned a value of 1 and other genotypes (homozygous and heterozygous for the lower estrogen exposure allele) were assigned 0. A score was created by adding the values. Women with four or five high estrogen variables were grouped because there were too few women with five high estrogen variables to assess separately (3 cases/4 controls).Notes: For each genotype, variants are listed in order of expected increasing estrogen (or progesterone for PGR-12) exposure:SHBG (rs6259) A allele is associated with higher SHBG levels. SHBG binds to estrogens and reduces their bioavailability. G allele = higher estrogen exposure.PGR-12 (rs1042838) T allele has been shown to reduce the PGR transcript stability and the response to progesterone. G allele = higher progesterone exposure.ESR1 (rs2234693) C allele may be associated with increased ERα transcription. C allele = possible higher exposure to estrogen signaling.CYP19 3′UTR (rs10046) T allele is associated with increased transcriptional activity of aromatase (converts androgens to estrogens). T allele = higher estrogen exposure.CYP19 5′Flank (rs4775936) A allele is associated with increased transcriptional activity of aromatase (converts androgens to estrogens). A allele = higher estrogen exposure.UGT1A1 (rs8175347) 7 repeat allele is associated with reduced glucuronidation (and clearance) of estrogens. 7 repeat allele = higher estrogen exposure.