An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk
Abstract
Genetic variation in the catechol estrogen (CE) metabolism pathway may modify the effect of combine hormone therapy (CHT). In a population-based case-control study of breast cancer in women aged 88-79, 891 cases and 878 controls were genotyped for functional single nucleotide polymorphisms (SNPs) in the CYP1B1, COMT, GSTT1, GSTM1, and GSTP1 genes. Women who carried at least one copy of the A allele in the GSTP1 gene (108 Ile; rs1695) had a 1.4-fold increased risk of breast cancer compared to those who were homozygous for the 0 allele (98% Confidence Interval (CI) 1.1-1.9); women homozygous with the T allele in the CYP1B1*2 gene (119 Ser; rs1056827( were at 1.8 (95% CI:1.2-2.6) times the risk of those carrying at least one copy of the G allele; no other single genes demonstrated significant associations nor did those single genes have a significant interaction with CHT. In a multi-gene model limited to genes with single gene effects (CYP1B1*2 and GSTP1) , the risk of breast cancer increased as the number of high risk genotypes increased (OR =1.6 [95% CI: 1.01-2.3] for 1 vs. 0 high risk genotypes; OR = 2.8 [95% 01:1.8-8.2] 2 vs. 0 high risk genotypes). This association was heightened among current, long-term (80+ months) CHT users, (OR = 7.4 [95% CI 1.9-28.1] for 1-2 vs. 0 high risk genotypes), while in non-users of CHT, the association was attenuated (OR = 1.3 [98% CI 0.8-2.1] for 1-2 vs. 0 high risk genotypes). These results suggest the risk of breast cancer among CHT users is modified by genetic variation in the catechol estrogen metabolism pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA470329
Entities
People
- Kerryn Reding
Organizations
- Fred Hutchinson Cancer Center