An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk
Annual rept. 15 Mar 2006-14 Mar 2007
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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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 CYP1B12 gene 119 Ser rs1056827 were at 1.8 95 CI1.2-2.6 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 CYP1B12 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 95 011.8-8.2 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.
- Medicine and Medical Research
- Organic Chemistry